bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation of alcoholic fatty liver and hepatic inflammation with a specific recall immune response in alcohol-consuming C57Bl/6 mice
Authors: Slukvin I I , Boor P J , Jerrells T R 
Published: March 2003

SummaryWhether immunological responses are involved in initiation and progression of alcoholic liver disease is unclear. We describe a mouse model of alcoholic liver injury characterized by steatosis and hepatic inflammation initiated by a recall immune response. Mice immune to Listeria monocytogenes fed a liquid diet containing ethanol and challenged with viable bacteria developed steatosis within 24 h and, at a later time, elevated serum alanine aminotransferase levels, indicating more liver damage in this group. Listeria antigen also induced steatosis and increased serum alanine aminotransferase levels in immune ethanol-consuming mice. The production of tumour necrosis factor by a recall immune response in this model is a major, but not the only, component in initiation of alcoholic liver disease.
Elongation factor 1 β/δ of Echinococcus granulosus and allergic manifestations in human cystic echinococcosis
Authors: Ortona E , Margutti P , Vaccari S , Riganò R , Profumo E , Buttari B , Chersi A , Teggi A , Siracusano A 
Published: March 2003

Summary
Allergic reactions, such as urticaria, itching and anaphylactic shock, often complicate the course of cystic echinococcosis (CE). To investigate the role of the IgE-immunoreactive recombinant Echinococcus granulosus elongation factor-1 β/δ (EgEF-1 β/δ) in the allergic disorders during CE we determined humoral and cell-mediated responses to this antigen in patients with CE grouped according to the clinical presence or absence of allergic reactions. Immunoblotting analysis showed that serum IgE-binding reactivity to EgEF-1 β/δ differed significantly in patients with and without allergic reactions (38 of 42, 90% vs. 31 of 56, 56%; P &lt; 10−4). EgEF-1 β/δ induced a proliferative response in 14 of 19 (74%) patients' peripheral blood mononuclear cells (PBMC) irrespective of the allergic manifestations and skewed Th1/Th2 cytokine activation towards a preferentially Th2 polarization. Epitope mapping identified an immunodominant epitope of 18 residues with 78% identity and 89% similarity with an IgE-immunoreactive Strongyloides stercoralis antigen. Overall these findings suggest that EgEF-1 β/δ is an allergenic molecule that may be a general marker of the intensity of CE immune response and that could lead to a deeper understanding of the specific antigen-induced mechanisms underlying allergic reactions in the human host.
γδT cells assistαβT cells in the adoptive transfer of contact hypersensitivity to para-phenylenediamine
Authors: Yokozeki H , Watanabe K , Igawa K , Miyazaki Y , Katayama I , Nishioka K 
Published: March 2003

SummaryPara-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2·5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2·5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1+, B220+, αβ TCR, γδ TCR, CD3, CD4, CD5+ and CD8. The in vitro treatment of effector cells with MoAbs against not only αβ TCR but also γδ TCR, together with complement, was found to diminish substantially the late response, elicited 12–24 h after challenge. γδ T cells reconstituted the ability of αβ T cells to transfer 24 h CHS responsiveness. The phenotype of the γδ T cells that assist CHS effector αβ T cells was CD3+, CD4 and CD8+ and these regulatory γδ T cells were neither Ag-specific nor MHC-restricted. Furthermore, γδ T cells from normal spleen could also assist αβ T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that αβ T cells strongly expressed mRNA IFN-γ, whereas γδ T cells expressed not only IFN-γ but also IL-4 and IL-10. These data indicate that not only early response cells and αβ T cells but also Th2 type γδ T cells may play an important role in the elicitation of CHS to PPD.
Cooperation of interleukin-17 and interferon-γon chemokine secretion in human fetal intestinal epithelial cells
Authors: Andoh A , Takaya H , Makino J , Sato H , Bamba S , Araki Y , Hata K , Shimada M , Okuno T , Fujiyama Y , Bamba T 
Published: March 2003

SummaryInterleukin (IL)-17 is a newly identified T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of IL-17 and interferon (IFN)-γ on chemokine secretion in human fetal intestinal epithelial cells. IL-8 and monocyte chemoattractant protein (MCP)-1 secretion by the human fetal intestinal epithelial cell line, intestine-407, was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analysed by a binding assay using [125I]-labelled IL-17. The activation of nuclear factor-κB (NF-κB), NF-IL6 and AP-1 was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The inducing effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h, and then gradually decreased. IL-17 and IFN-γ synergistically increased IL-8 and MCP-1 secretion and mRNA abundance. IFN-γ induced a weak increase in IL-17 R mRNA abundance, and incubation with IFN-γ for 24 h enhanced [125I]-labelled IL-17-binding by 2·4-fold. IL-17 rapidly induced the phosphorylation and degradation of IκBα molecules, and the combination of IL-17 and IFN-γ induced a marked increase in NF-κB DNA-binding activity as early as 1·5 h after the stimulation. Furthermore, this combination induced an increase in NF-IL-6 and AP-1 DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells. The combination of IL-17 with IFN-γ synergistically enhanced chemokine secretion. These effects of IL-17 and IFN-γ might play an important role in the inflammatory responses in the intestinal mucosa.
Prevention of adjuvant arthritis by the W3/25 anti-CD4 monoclonal antibody is associated with a decrease of blood CD4+CD45RChigh T cells
Authors: Pelegrí C , Castell M , Serra M , Rabanal M , Rodríguez-Palmero M , Castellote C , Franch A 
Published: March 2003

SummaryImbalance between Th1 and Th2 functions is considered to play a key role in the induction and development of several autoimmune diseases, and the correction of that imbalance has led to effective therapies of some experimental pathologies. To examine whether CD4+CD45RChigh (Th1-like) and CD4+CD45RClow (Th2-like) lymphocytes play a role in the pathogenesis of adjuvant arthritis (AA) and in its prevention by anti-CD4 antibody, CD45RC expression on CD4+ T cells was determined in arthritic rats and in animals treated with an anti-CD4 MoAb (W3/25) during the latency period of AA. The phenotype of regional lymph node lymphocytes from arthritic rats in the active phase of the disease was determined by flow cytometry. Peripheral blood lymphocytes from rats treated with W3/25 MoAb were also analysed for 2 weeks after immunotherapy finished. IgG2a and IgG1 isotypes of sera antibodies against the AA-inducing mycobacteria, considered to be associated with Th1 and Th2 responses, respectively, were also determined by ELISA techniques. Fourteen days after arthritis induction, regional lymph nodes presented an increase in CD4+CD45RChigh T cell proportion. Preventive immunotherapy with W3/25 MoAb inhibited the external signs of arthritis and produced a specific decrease in blood CD4+CD45RChigh T cells and a diminution of antibodies against mycobacteria, more marked for IgG2a than for IgG1 isotype. These results indicate a possible role of CD4+CD45RChigh T lymphocytes in the pathogenesis of AA, and suggest that the success of anti-CD4 treatment is due to a specific effect on CD4+CD45RChigh T subset that could be associated with a decrease in Th1 activity.
C1q-bearing immune complexes induce IL-8 secretion in human umbilical vein endothelial cells (HUVEC) through protein tyrosine kinase- and mitogen-activated protein kinase-dependent mechanisms: evidence that the 126 kD phagocytic C1q receptor mediates immune complex activation of HUVEC
Authors: Xiao S , Xu C , Jarvis J N 
Published: March 2003

SummaryEndothelial cells play a pivotal role in the initiation and perpetuation of inflammation. C1q, the first component of the classical pathway of complement, is a potent stimulus leading to endothelial cell activation and cytokine production. The specific cellular mechanisms through which endothelial cells are stimulated by C1q are not known. We stimulated human umbilical vein endothelial cells (HUVEC) with either monomeric C1q or C1q-bearing immune complexes (C1q-IC) in the presence or absence of inhibitors of protein tyrosine kinases (PTK) or mitogen-activated protein kinases (MAPK). C1q-IC, but not monomeric C1q, induced IL-8 production in dose- and time-dependent fashion. R3, a cross-linking monoclonal IgM antibody against the126 kD phagocytic C1q receptor (C1qR), also stimulated IL-8 production. IL-8 mRNA accumulation was detected by Northern blot analysis within 2 h of stimulation by the immune complexes and was enhanced by the addition of cycloheximide. Secretion of IL-8 by C1q-IC stimulated HUVEC was completely blocked by the PTK inhibitor, genistein or the MAPK inhibitor, UO126. These experiments demonstrate that C1q-IC-induced production of IL-8 in HUVEC is dependent upon the activation of PTK and MAPK. These findings also support a role for the phagocytic C1qR as an important activator of HUVEC by immune complexes.
Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset activation
Authors: Arrington J L , Chapkin R S , Switzer K C , Morris J S , McMurray D N 
Published: March 2003

SummaryStudies in humans and murine disease models have clearly shown dietary fish oil to possess anti-inflammatory properties, apparently mediated by the n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To determine the mechanisms by which dietary EPA and DHA modulate mouse T-cell activation, female C57BL/6 mice were fed diets containing either 2% safflower oil (SAF), 2% fish oil (FO), or a 2% purified EPA/DHA ethyl ester mixture for 14 days. Splenic CD4 T cells (∼90% purity) or CD8 T cells (∼85% purity) were incubated with agonists which act at the plasma membrane receptor level [anti(α)-CD3/anti(α)-CD28], the intracellular level (PMA/Ionomycin), or at both the receptor and intracellular levels (αCD3/PMA). CD4 T cells stimulated with αCD3/αCD28 or PMA/Ionomycin proliferated and produced principally IL-2 (i.e. a Th1 phenotype), whereas the proliferation of CD4 T cells stimulated with αCD3/PMA was apparently driven principally by IL-4 (i.e. a Th2 phenotype). The IL-4 driven proliferation of putative Th2 CD4 cells was enhanced by dietary n-3 fatty acids (P = 0·02). Conversely, IL-2 production by αCD3/α CD28-stimulated CD4 T cells was reduced in FO-fed animals (P &lt; 0·0001). The αCD3/αCD28-stimulated CD8 cells cultured from FO-fed animals exhibited a significant decrease (P &lt; 0·05) in proliferation. There were no dietary effects seen in αCD3/PMA-stimulated CD8 cells, which produced both IL-2 and IL-4, or in PMA/Ionomycin-stimulated CD8 cells, which produced principally IL-2. These data suggest that dietary n-3 fatty acids down-regulated IL-2 driven CD4 and CD8 activation, while up-regulating the activation of the Th2 CD4 T-cell subset. Thus, the anti-inflammatory effects of n-3 fatty acids may result in both the direct suppression of IL-2-induced Th1 cell activation and the indirect suppression of Th1 cells by the enhanced cross-regulatory function of Th2 cells.
IFN-γsynergizes with TNF-αbut not with viableH. pyloriin up-regulating CXC chemokine secretion in gastric epithelial cells
Authors: Kraft M , Riedel S , Maaser C , Kucharzik T , Steinbuechel A , Domschke W , Luegering N 
Published: March 2003

SummaryHelicobacter pylori colonizes the gastric epithelial surface and induces epithelial cells to increase production of the neutrophil attractant IL-8. Little is known about the role of the gastric epithelium in regulating mucosal T cell trafficking. We therefore characterized constitutive and regulated epithelial expression of the CXC chemokines IP-10, I-TAC and Mig, which specifically attract CXCR3 expressing CD4+ T cells. Human gastric epithelial cell lines (AGS, Kato III, NCI) were used to characterize the constitutive and regulated expression of three CXC chemokines in response to IFN-γ, TNF-α and different H. pylori preparations. Chemokine mRNA and protein production were measured by RT-PCR and ELISA. Gastric epithelial cells constitutively expressed mRNA for IP-10, Mig and I-TAC. IFN-γ in combination with TNF-α strongly induced secretion of those chemokines. Soluble or membranous fractions of H. pylori significantly inhibited IFN-γ/TNF-α induced epithelial cell IP-10 and Mig production. Gastric epithelial cells may contribute to mucosal T cell trafficking. The capacity of H. pylori products to inhibit IP-10 and Mig secretion may explain, at least in part, the failure to induce protective immunity against this bacterium and the ability of H. pylori to affect the presentation of the local inflammation.
CD45RA and CD45RO isoforms in infected malnourished and infected well-nourished children
Authors: Nájera O , González C , Toledo G , López L , Cortés E , Betancourt M , Ortiz R 
Published: March 2003

Summary
The aim of this study was to determine if the distribution in vivo of CD4+CD45RA+/CD45RO− (naive), CD4+CD45RA+/CD45RO+ (Ddull) and CD4+CD45RO+ (memory) lymphocytes differs in malnourished infected and well-nourished infected children. The expression of CD45RA (naive) and CD45RO (memory) antigens on CD4+ lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 15 malnourished infected, 12 well-nourished infected and 10 well-nourished uninfected children. Malnourished infected children showed higher fractions of Ddull cells (11·4 ± 0·7%) and lower fractions of memory cells (20·3 ± 1·7%) than the well-nourished infected group (8·8 ± 0·8 and 28·1 ± 1·8%, respectively). Well-nourished infected children showed increased percentages of memory cells, an expected response to infection. Impairment of the transition switch to the CD45 isoforms in malnourished children may explain these findings, and may be one of the mechanisms involved in immunodeficiency in these children.
Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA): possible involvement of complement in granulocyte cytotoxicity
Authors: Akamizu T , Ozaki S , Hiratani H , Uesugi H , Sobajima J , Hataya Y , Kanamoto N , Saijo M , Hattori Y , Moriyama K , Ohmori K , Nakao K 
Published: March 2003

SummaryAlthough antineutrophil antibodies are thought to be involved in drug-induced neutropenia, neither the precise mechanisms nor the particular antigens on the neutrophil surface have yet been clarified. Recently, we examined a patient with Graves’ disease who developed antineutrophil cytoplasmic antibodies (ANCA) after propylthiouracil treatment and exhibited neutropenia. Because several target antigens of ANCA are expressed on the surface of neutrophils, it was suggested that ANCA might contribute to neutropenia. The patient’s serum bound specifically to neutrophils and HL-60 cells differentiated into granulocytes, and lysed the HL-60 cells via a complement-mediated mechanism. Furthermore, two representative ANCA antigens, proteinase 3 and myeloperoxidase, significantly inhibited both the binding and cytotoxicity of the serum. Finally, tumour necrosis factor-α, which is known to up-regulate cell surface expression of several ANCA antigens, enhanced both the binding and cytotoxicity of the serum. These findings suggest that ANCA induced by propylthiouracil contributed to leucopenia through a complement-mediated mechanism.
Analysis of the B cell repertoire against autoantigens in patients with giant cell arteritis and polymyalgia rheumatica
Authors: SCHMITS R , KUBUSCHOK B , SCHUSTER S , PREUSS K-D , PFREUNDSCHUH M 
Published: March 2003

Summary
The analysis of the antibody repertoire of patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) might identify target antigens of the autoimmune response with potential relevance to our understanding of the pathogenesis of the disease and to the development of serodiagnostic tests. To detect such antigens, we screened a cDNA library derived from normal human testis for antigens reacting with IgG antibodies in the 1 : 250 diluted sera of three patients with untreated GCA using SEREX, the serological identification of antigens by recombinant cDNA expression cloning. Of 100 000 clones screened with each serum, six, 28 and six clones, respectively, were positive, representing a total of 33 different antigens. Most of the antigens reacted only with the serum used for identification and/or at a similar frequency with normal control sera. However, lamin C and the nuclear antigen of 14 kD reacted specifically with 32% of GCA/PMR, but with none of the control sera, while human cytokeratin 15, mitochondrial cytochrome oxidase subunit II, and a new gene product were detected preferentially, but not exclusively by sera from GCA/PMR patients. We conclude that patients with GCA/PMR develop antibodies against a broad spectrum of human autoantigens. Antibodies against human lamin C, the nuclear autoantigen of 14 kD as well as human cytokeratin 15, mitochondrial cytochrome oxidase subunit II and the product of a new gene should be investigated further to determine their value as tools for the diagnosis and/or the definition of clinical subgroups of patients with GCA/PMR.
Treatment of autoimmune diabetes recurrence in non-obese diabetic mice by mouse interferon-βin combination with an analogue of 1α,25-dihydroxyvitamin-D3
Authors: GYSEMANS C , VAN ETTEN E , OVERBERGH L , VERSTUYF A , WAER M , BOUILLON R , MATHIEU C 
Published: March 2003

SUMMARYAutoimmune diabetes recurrence is in part responsible for islet graft destruction in type 1 diabetic individuals. The aim of the present study was to design treatment modalities able to prevent autoimmune diabetes recurrence after islet transplantation in spontaneously diabetic NOD mice. In order to avoid confusion between autoimmune diabetes recurrence and allograft rejection, we performed syngeneic islet transplantations in spontaneously diabetic NOD mice. Mice were treated with mouse interferon-β (IFN-β, 1 × 105 IU/day), a new 14-epi-1,25-(OH)2D3-analogue (TX 527, 5 μg/kg/day) and cyclosporin A (CsA, 7·5 mg/kg/day) as single substances and in combinations. Treatment was stopped either 20 days (IFN-β and CsA) or 30 days (TX 527) after transplantation. Autoimmune diabetes recurred in 100% of control mice (MST 11 days). None of the mono-therapies significantly prolonged islet graft survival. Combining CsA with TX 527 maintained graft function in 67% of recipients as long as treatment was given (MST 31 days, P &lt; 0·01 versus controls). Interestingly, 100% of the IFN-β plus TX 527-treated mice had normal blood glucose levels during treatment, and even had a more pronounced prolongation of graft survival (MST 62 days, P &lt; 0·005 versus controls). Cytokine mRNA analysis of the grafts 6 days after transplantation revealed a significant decrease in IL-2, IFN-γ and IL-12 messages in both IFN-β plus TX 527- and CsA plus TX 527-treated mice, while only in the IFN-β with TX 527 group were higher levels of IL-10 transcripts observed. Therefore, we conclude that a combination of IFN-β and TX 527 delays autoimmune diabetes recurrence in islet grafts in spontaneously diabetic NOD mice.
Spontaneous production of RANTES and antigen-specific IFN-γ production in macaques vaccinated with SHIV-4 correlates with protection against SIVsm challenge
Authors: AHMED R K S , MÄKITALO B , KARLÉN K , NILSSON C , BIBERFELD G , THORSTENSSON R 
Published: March 2003

SUMMARY
The β-chemokines, RANTES, MIP-1α and MIP-1β, have been implicated as being some of the protective factors in the immune response against human immunodeficiency virus (HIV) infection. We have presented data previously indicating that these chemokines also play a role in protective immunity against HIV/SIV infection in macaques. The aim of this study was to investigate the production of β-chemokines in eight cynomolgus macaques vaccinated with non-pathogenic SHIV-4 in relation to protection against pathogenic SIVsm challenge. Four control animals were also included in the study. Two of the vaccinated monkeys were completely protected and one was partially protected against the challenge virus. The monkeys that resisted infectious SIVsm virus challenge showed higher spontaneous β-chemokine production by peripheral blood mononuclear cells and had higher numbers of antigen-induced IFN-γ secreting cells compared to the non-protected animals. Our observations support our previous findings that the genetic background of the host and/or environmental factors are involved in the chemokine production and that β-chemokines contribute to protection against HIV/SIV infection.
In vivo activated T cells in rheumatoid synovitis. Analysis of Th1- and Th2-type cytokine production at clonal level in different stages of disease
Authors: GERLI R , BISTONI O , RUSSANO A , FIORUCCI S , BORGATO L , CESAROTTI M E F , LUNARDI C 
Published: March 2003

SUMMARY
T-cell cytokines play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). Their detection in the joint, however, is impaired by the complex network present in the synovium. Although many synovial T cells show signs of previous activation, only a few express interleukin (IL)-2 receptor, marker of recent activation. The aim of this study was to analyse the cytokine production by in vivo activated (IL-2R +) T cells from RA at different stages of the disease. For this purpose, T cells were isolated from peripheral blood and synovial fluid of four patients with active RA, two at the onset of the disease, one in the early phase during treatment, one in long-lasting chronic phase. One patient was studied at the onset of the disease and 52 months later. Cells were initially expanded with a low dose of IL-2, cloned and analysed for cytokine production. The results showed a strong predominance of T helper (Th) 1 clones in the blood and a slight prevalence of Th0 clones in the joint of all the four patients. Interferon-γ and IL-2 production was higher in the long-lasting RA, whereas IL-4 synthesis was prevalent in early RA. Enrichment in IL-10-producing clones was present only in the joint of the untreated patients. The longitudinal study confirmed the differences in cytokine production between early and late phases of disease. These data confirm that RA is mainly a Th1-driven condition. However, in vivo activated synovial T cells produce also Th2-type anti-inflammatory cytokines, such as IL-4 and IL-10. The synthesis of both cytokines is a feature of the very early phase of RA, although the selective recruitment of IL-10-producing T cells is quickly lost.