bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemokines in cutaneous wound healing
Authors: Gillitzer Reinhard , Goebeler Matthias 
Published: September 2022

AbstractHealing of wounds is one of the most complex biological events afterbirth as a result of the interplay of different tissue structures and alarge number of resident and infiltrating cell types. The latter aremainly constituted by leukocyte subsets (neutrophils, macrophages, mastcells, and lymphocytes), which sequentially infiltrate the wound siteand serve as immunological effector cells but also as sources ofinflammatory and growth-promoting cytokines. Recent data demonstratethat recruitment of leukocyte subtypes is tightly regulated bychemokines. Moreover, the presence of chemokine receptors on residentcells (e.g., keratinocytes, endothelial cells) indicates thatchemokines also contribute to the regulation of epithelialization,tissue remodeling, and angiogenesis. Thus, chemokines are in anexclusive position to integrate inflammatory events and reparativeprocesses and are important modulators of human-skin wound healing.This review will focus preferentially on the role of chemokines duringskin wound healing and intends to provide an update on the multiplefunctions of individual chemokines during the phases of woundrepair.
NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer
Authors: Suzuki Kazuhiro , Nakazato Haruki , Matsui Hiroshi , Hasumi Masaru , Shibata Yasuhiro , Ito Kazuto , Fukabori Yoshitatsu , Kurokawa Kohei , Yamanaka Hidetoshi 
Published: September 2022

AbstractInterleukin (IL)-15 is a pleiotropic cytokine that is important forinnate and adaptive immune cell homeostasis. The expression of IL-15protein is controlled by posttranscriptional mechanisms. Here, weconstructed a human IL-15 expression vector consisting of the humanIL-2 signal peptide, the human IL-15 mature peptide-coding sequences,and an out-of-frame human growth hormone gene. Human prostate cancercells, PC-3, transfected with this highly secretable form of the IL-15gene, successfully secreted abundant bioactive IL-15 protein. In nudemice, the growth of PC-3 cells producing IL-15 was remarkably retarded.NK cell-depletion using anti-asialo GM1 antibody restoredtumorigenicity. Histologically, tumors derived from IL-15-producingPC-3 cells contained necrotic areas with high apoptotic index.Splenocytes incubated with supernatant of transfectants killed targetPC-3 cells and expressed a significantly high level of mIFN-γ mRNA.These observations suggest that NK cell-mediated, anti-tumor effects ofIL-15 could provide a potential rationale for gene therapy of prostatecancer.
Ovalbumin aerosols induce airway hyperreactivity in naïve DO11.10 T cell receptor transgenic mice without pulmonary eosinophilia or OVA-specific antibody
Authors: Wilder Julie A , Collie David S , Bice David E , Tesfaigzi Yohannes , Lyons C Richard , Lipscomb Mary F 
Published: September 2022

AbstractThe pathobiology of allergic asthma is being studied using murine models, most of which use systemic priming followed by pulmonary challenges with the immunizing antigen. In general, mice develop eosinophilic pulmonary inflammation, increased antigen-specific immunoglobulins, and airway hyperreactivity (AHR), all of which are dependent on antigen-specific T cell activation. To establish a model of allergic asthma, which did not require systemic priming, we exposed DO11.10 T cell receptor transgenic mice, which have an expanded repertoire of ovalbumin (OVA), peptide-specific T cells, to limited aerosols of OVA protein. DO11.10 +/− mice developed AHR in the absence of increases in total serum IgE, OVA-specific IgG, or eosinophilia. The AHR was accompanied by pulmonary recruitment of antigen-specific T cells with decreased expression of CD62L and CD45RB and increased expression of CD69, a phenotype indicative of T cell activation. Our results support recent hypotheses that T cells mediate AHR directly.
UVB-irradiated dendritic cells are impaired in their APC function and tolerize primed Th1 cells but not naive CD4+ T cells
Authors: Denfeld Ralf W , Hara Hisamichi , Tesmann Jens P , Martin Stefan , Simon Jan C 
Published: September 2022

AbstractWe have shown that low-dose UVB radiation converts Langerhans cells(LC) from immunogenic to tolerogenic APC. Therefore, we questionedwhether low-dose UVB irradiation of bone marrow-derived dendritic cells(DC) alters their APC function, thereby inducing tolerance in T cells.To address this issue, cocultures of DC; and naïve, allogeneicT cells; naïve, OVA-specific TCR-transgenic T cells fromDO11.10 mice; or primed, antigen-specific T cells using the Th1 cloneAE7 were analyzed. First, we found low-dose UVB-irradiated DC(UVB-DC) to dose-dependently (50–200 J/m2) inhibit T-cellproliferation of naive and primed T cells. In addition, supernatantsharvested from cocultures of UVB-DC and naive T cells showed markedlyreduced levels of IL-2 and IFN-γ and to a lesser degree of IL-4 andIL-10, suggesting a preferential down-regulation of Th1 responses byUVB-DC. FACS analysis of UVB-DC revealed no changes in surfaceexpression of MHC, costimulatory, and adhesion molecules. To testtolerance induction, allo- or antigen-specific T cells isolated fromcocultures with unirradiated DC and UVB-DC were restimulated withunirradiated DC or IL-2. It is interesting that UVB-DC inducedantigen-specific tolerance in the Th1 clone AE7. In contrast, UVB-DCinduced a partial inhibition of allogeneic T-cell proliferation but notolerance with similar unresponsiveness to restimulation with IL-2 andunirradiated DC irrespective of their haplotype. Similar observationswere made when naïve, TCR-transgenic T cells from DO11.10 micewere used. In conclusion, UVB-DC are impaired in their APC function andtolerize the primed antigen-specific Th1 clone AE7 but not naive allo-or OVA-specific T cells.
Expression and function of galectin-3, a β-galactoside-binding protein in activated T lymphocytes
Authors: Joo Hong-Gu , Goedegebuure Peter S , Sadanaga Noriaki , Nagoshi Makoto , von Bernstorff Wolfram , Eberlein Timothy J 
Published: September 2022

AbstractA soluble beta-galactoside-binding lectin, galectin-3 has been shown tobe involved in cell adhesion and activation of immune cells. Althoughgalectin-3 is known to be expressed in various types of cells, it hasnot been shown whether galectin-3 is expressed in T lymphocytes. Wepresent evidence here that galectin-3 is expressed in activated murineT lymphocytes including CD4+ and CD8+ T cellsbut not in resting T cells. Galectin-3 expression was induced byanti-CD3 mAb or mitogen and enhanced by common γ-chain signalingcytokines, IL-2, IL-4, and IL-7, in activated T lymphocytes, whereasthe inflammatory cytokines including TNF-α and IFN-γ did not.Galectin-3 expression and proliferation were down-regulated bywithdrawal of IL-2 and gamma irradiation. Anti-sense but not sensephosphorothioated oligonucleotides for galectin-3 inhibited galectin-3expression and blocked proliferation of T cells significantly. Thisstudy suggests that up-regulation of galectin-3 plays an important rolein proliferation of activated T lymphocytes.
CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells regulates shear-resistant leukocyte rolling vial-selectin
Authors: Li Xuan , Tu LiLi , Murphy Patricia G , Kadono Takafumi , Steeber Douglas A , Tedder Thomas F 
Published: September 2022

AbstractSulfation is an essential component of the selectin ligands, potentially mediated by members of a new family of carbohydrate sulfotransferases. In this study, we assessed the contributions of CHST1, CHST2, CHST3, and CHST4 in producing functional l-selectin ligands. Human umbilical vein endothelial cells predominantly expressed CHST1 and CHST2 transcripts with low levels of CHST3 mRNA, while cytokine activation up-regulated CHST2 expression and induced low-level CHST4 expression. A human umbilical vein endothelial cell line, EA.hy926, displayed functional l-selectin ligands that correlated with CHST1 and CHST2 expression in the absence of CHST4 expression. Increased CHST1 or CHST2 expression by a cell line expressing low-level l-selectin ligand activity during in vitro flow chamber assays increased rolling leukocyte numbers, reduced rolling velocities, and enhanced leukocyte rolling under higher shear stresses. These results suggest that CHST1 and CHST2 contribute to the generation of optimal l-selectin ligands in vascular endothelial cells at sites of inflammation.
The collagenous domain of class A scavenger receptors is involved in macrophage adhesion to collagens
Authors: Gowen Brian B , Borg Thomas K , Ghaffar Abdul , Mayer Eugene P 
Published: September 2022

AbstractClass A macrophage scavenger receptors (MSRs) have a remarkably broadligand specificity and are well-known for their roles in atherogenesisand host defense. Recently, we demonstrated that these receptors alsorecognize and mediate adhesion to denatured forms of type I collagen. In this study, the involvement of the collagenous domain of MSRs inbinding to denatured type I collagen was investigated. Transientexpression of full-length, native type II MSR in COS-1 cells conferredadhesion to denatured type I collagens, whereas expression of atruncated receptor lacking the distal portion of the collagenous domaindid not. Further, a synthetic peptide derived from the collagenousdomain was effective in abrogating Mφ adhesion to denatured forms oftype I collagen. We also addressed collagen-type specificity byexamining MSR affinity for type III and type IV collagens. As with typeI collagen, Mφs adhered only to denatured forms of type III collagen.Moreover, the adhesion was mediated by MSRs. In contrast, adhesion todenatured type IV collagen was not shown to be MSR-dependent, butadhesion to the native form was. MSR-mediated adhesion to types III andIV collagens was also shown to be dependent on the collagenous domain.Taken together, these data strongly suggest that the collagenous domainis involved in MSR-mediated adhesion to denatured forms of types I andIII collagens and native, but not denatured, type IV collagen.
Transforming growth factor-β suppresses tumor necrosis factor α-induced matrix metalloproteinase-9 expression in monocytes
Authors: Vaday Gayle G , Schor Hagai , Rahat Michal A , Lahat Nitza , Lider Ofer 
Published: September 2022

AbstractThe inflammatory response is marked by the release of several cytokines with multiple roles in regulating leukocyte activities, including the secretion of matrix metalloproteinases (MMPs). Although the effects of individual cytokines on monocyte MMP expression have been studied extensively, few studies have examined the influence of combinations of cytokines, which are likely present at inflammatory sites. Herein, we report our investigation of the combinatorial effects of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β on MMP-9 synthesis. We found that TGF-β suppressed TNF-α-induced MMP-9 secretion by MonoMac-6 monocytic cells in a dose-dependent manner, with a maximal effect of TGF-β observed at 1 ng/ml. Such suppression was likely regulated at the pretranslational level, because steady-state mRNA levels of TNF-α-induced MMP-9 were reduced by TGF-β, and pulse-chase radiolabeling also showed a decrease in new MMP-9 protein synthesis. The suppressive effects of TGF-β were time dependent, because short exposures to TNF-α before TGF-β or simultaneous exposure to both cytokines efficiently reduced MMP-9 secretion. Expression of the tissue inhibitor of metalloproteinases (TIMP)-1 and TNF-α receptors was unaffected by either cytokine individually or in combination. Affinity binding with radiolabeled TGF-β demonstrated that levels of TGF-β receptors were not increased after preincubation with TGF-β. Suppression of TNFα-induced MMP-9 secretion by TGF-β correlated with a reduction in prostaglandin E2 (PGE2) secretion. Furthermore, the effect of TGF-β or indomethacin on blockage of TNF-α-stimulated MMP-9 production was reversed by the addition of either exogenous PGE2 or the cyclic AMP (cAMP) analogue Bt2cAMP. Thus, we concluded that TGF-β acts as a potent suppressor of TNF-α-induced monocyte MMP-9 synthesis via a PGE2- and cAMP-dependent mechanism. These results suggest that various combinations of cytokines that are present at inflammatory sites, as well as their balance during different stages of inflammation, may provide the signals necessary for directing MMP-mediated leukocyte activities.
Expression of the apolipoprotein C-II gene during myelomonocytic differentiation of human leukemic cells
Authors: Chun Eun Mi , Park Young Jae , Kang Hong Soon , Cho Hyun Min , Jun Do Youn , Kim Young Ho 
Published: September 2022

AbstractApolipoprotein C-II (apoC-II), which is known to activate lipoprotein lipase (LPL), was identified by ordered differential display (ODD)-polymerase chain reaction (PCR) as a cDNA fragment exhibiting a distinct increase in expression during 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced differentiation of promonocytic U937 cells into monocytes and macrophages. The amount of apoC-II mRNA expression detectable in U937 cells significantly increased and reached a maximum 24–48 h after treatment with 32 nM TPA. apoC-II mRNA was also detected in monocytic THP-1 cells but was not detected in promyelocytic HL-60 cells. In healthy human tissues, the most significant expression of apoC-II mRNA was in the liver. Although apoC-II mRNA expression was markedly up-regulated during the induced differentiation of HL-60 cells into monocytes and macrophages with 32 nM TPA, such expression was not induced during the differentiation of HL-60 cells into granulocytes with 1.25% dimethyl sulfoxide. These results suggest that human apoC-II expression is induced at the transcription level during myelomonocytic differentiation and may confer an important role to macrophages involved in normal lipid metabolism and atherosclerosis.
Involvement of PKA, PKC, and Ca2+ in LPS-activated expression of the chicken lysozyme gene
Authors: Regenhard Petra , Goethe Ralph , Phi-van Loc 
Published: September 2022

AbstractThe lysozyme gene is activated in myelomonocytic HD11 cells in response to LPS. In this study, we described the involvement of LPS-activated signal transduction pathways in activation of the lysozyme gene. Pre-treatment of HD11 cells with H-89, H-7, TMB-8, or KN-93 resulted in inhibition of the LPS-enhanced lysozyme expression, suggesting that PKA, PKC, and Ca2+-dependent protein kinases participate in the LPS activation. CaMKII seems to be required for the processing of lysozyme transcripts. TPA and calcium ionophore A23187, when separately added to HD11 cells, stimulated the lysozyme expression effectively, and forskolin was ineffective. It is interesting that simultaneous treatment of cells with forskolin and calcium ionophore A23187 resulted in a potentiated increase in lysozyme mRNA expression, indicating a synergistic cooperation of PKA and Ca2+. This synergistic effect of PKA and Ca2+ was observed on the expression of a stably integrated CAT construct, controlled by the lysozyme promoter and the −6.1-kb enhancer containing binding sites for C/EBP and NF-κB/Rel. Therefore, we discussed the role of C/EBPβ(NF-M), CREB, and NF-κB/Rel as possible targets for phosphorylation mediated by PKA, PKC, and Ca2+.
Signal transduction pathways for activation of extracellular signal-regulated kinase by arachidonic acid in rat neutrophils
Authors: Chang Ling-Chu , Wang Jih-Pyang 
Published: September 2022

AbstractPhosphorylation of extracellular signal-regulated kinase (ERK) inresponse to arachidonic acid (AA) was rapid and transient, peaking at 1min and disappearing after 3 min, and it was accompanied by an increasein ERK activity in rat neutrophils. We examined the upstream regulationof AA-stimulated ERK activation using one of the following signalingpathway inhibitors to pretreat rat cells: the ERK kinase inhibitorU0126 or PD98059, the Gi/o inhibitor pertussis toxin (PTX),the tyrosine kinase inhibitor genistein, the phosphatidylinositol3-kinase (PI3K) inhibitor wortmannin or LY294002, the Ca2+chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, or the phospholipase C(PLC) inhibitor U73122. All of these inhibitors attenuated AA-inducedERK activation. Activation of ERK was also effectively attenuated bythe cyclooxygenase and lipoxygenase inhibitor BW755C and by theleukotriene biosynthesis inhibitor MK886, but the cyclooxygenaseinhibitor indomethacin did not attenuate ERK activation. After exposingcells to three distinct protein kinase C (PKC) inhibitors, we foundthat Gö6976 significantly attenuated ERK phosphorylation butpotentiated ERK activity. Neither Gö6983 nor GF109203Xaffected AA-induced responses. These data suggest that the lipoxygenasemetabolite(s) produced mediates AA-stimulated ERK activation and thatthis effect is upstream regulated by PT-sensitive G protein,nonreceptor tyrosine kinase, PI3K, and PLC/Ca2+ signalingpathways in rat neutrophils.
Analysis of macrophage activation in African trypanosomiasis
Authors: Paulnock Donna M , Coller Susan P 
Published: September 2022

AbstractAfrican trypanosomes cause a fatal disease of man and animals that ischaracterized by extensive functional, histological, and pathologicalchanges in the lymphoid tissues of infected hosts, including anincrease in the numbers and activation state of macrophages. Macrophageactivation during infection is the result of exposure of these cells toparasite components and host-derived IFN-γ, produced in response toparasite antigens. The balance of these different activation signalsmay determine the outcome of infection. In the experiments describedhere, we assessed the ability of the variant surface glycoprotein (VSG)of the organism Trypanosoma brucei rhodesiense (T.b.rhodesiense) to activate macrophages directly. Our resultsdemonstrate that macrophages bind and are activated by the VSGmolecule. The resulting profile of activation differs from thatstimulated by IFN-γ. These results suggest that the interaction ofhost macrophages with VSG released during parasite infection may be akey component of trypanosomiasis.
Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37)
Authors: Yang De , Chertov Oleg , Oppenheim Joost J 
Published: September 2022

AbstractDefensins and cathelicidins are the two major families of mammalian anti-microbial proteins. They contribute to host, innate, anti-microbial defense by disrupting the integrity of the bacterial cell membrane. However, several members of the mammalian anti-microbial proteins including defensins and cathelicidins have been shown recently to have chemotactic effects on host cells. Human neutrophil α-defensins are chemotactic for resting, naïve CD45RA/CD4 T cells, CD8 T cells, and immature dendritic cells. Human β-defensins are also chemotactic for immature dendritic cells but induce the migration of memory CD45RO/CD4 T cells. In contrast, cathelicidin/LL-37 is chemotactic for neutrophils, monocytes, and T cells but not for dendritic cells. Thus, these anti-microbial peptides have distinct, host-target cell spectra. The chemotactic activities of human β-defensins and cathelicidin/LL-37 are mediated by human CC chemokine receptor 6 and formyl peptide receptor-like 1, respectively. The capacities of defensins and cathelicidins to mobilize various types of phagocytic leukocytes, immature dendritic cells, and lymphocytes, together with their other effects such as stimulating IL-8 production and mast cell degranulation, provide evidence for their participation in alerting, mobilizing, and amplifying innate and adaptive anti-microbial immunity of the host.
In vivo roles of donor and host dendritic cells in allogeneic immune response: cluster formation with host proliferating T cells
Authors: Saiki Takahito , Ezaki Taichi , Ogawa Michio , Maeda Keiko , Yagita Hideo , Matsuno Kenjiro 
Published: September 2022

AbstractPossible roles of dendritic cells (DCs) in allogeneic immune responses in host lymphoid tissues were characterized in situ by using rat DC transfer and cardiac transplantation models. When allogeneic DCs were intravenously injected, these cells selectively migrated to the T-cell area of hepatic lymph nodes, with peak accumulation at 18 h after injection. Donor DCs and proliferating host T cells formed clusters (rosettes) in which the T-cell proliferative response started. The donor DCs were CD80+ CD86+ and, ultrastructurally, were in intimate contact with lymphoblasts within the rosettes. As a novel finding, some of the migrated donor DCs were quickly phagocytosed by putative host interdigitating DCs. By 48 h, the remaining donor DCs had disintegrated within the rosettes. Host interdigitating DCs also formed rosettes throughout the T-cell area, and their kinetics correlated well with that of the T-cell proliferation. In the cardiac allograft model, a few donor DCs selectively migrated to the host spleen and hepatic nodes. Rosette formation by donor and host DCs, phagocytosis of donor DCs, and the T-cell proliferative response occurred in much the same fashion as they did in the first experiment. We conclude that the donor rosettes at the early stage represent the sites of direct allosensitization and those at the late stage represent donor-DC killing. Host rosettes are the sites of T-cell proliferation. In this structure, phagocytosed donor-DC-derived antigens are presumably indirectly presented.
CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus
Authors: Exley Mark A , Bigley Nancy J , Cheng Olivia , Tahir Syed Muhammad Ali , Smiley Stephen T , Carter Quincy L , Stills Harold F , Grusby Michael J , Koezuka Yasuhiko , Taniguchi Masuru , Balk Steven P 
Published: September 2022

AbstractA subset of CD161 (NK1) T cells express an invariant Vα14Jα281TCR-α chain (Vαinvt T cells) and produce Th2 and Th1cytokines rapidly in response to CD1d, but their physiologicalfunction(s) remain unclear. We have found that CD1d-reactive T cellsmediate to resistance against the acute, cytopathic virus diabetogenicencephalomyocarditis virus (EMCV-D) in relatively Th1-biased,C57BL/6-based backgrounds. We show now that these results generalize toTh2-biased, hypersensitive BALB/c mice. CD1d-KO BALB/c mice were moresusceptible to EMCV-D. Furthermore, α-galactosylceramide(α-GalCer), a CD1d-presented lipid antigen that specificallyactivates Vαinvt T cells, protected wild-type (WT) miceagainst EMCV-D-induced encephalitis, myocarditis, and diabetes. Incontrast, neither CD1d-KO nor Jα281-KO mice were protected byα-GalCer. Finally, disease in Jα281-KO mice was comparable to WT, indicating for the first time equivalent roles for CD1d-reactiveVαinvt and noninvariant T cells in resistance to acuteviral infection. A model for how CD1d-reactive T cells can initiateimmune responses, which synthesizes current results, ispresented.