The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide
Authors: Gaetano Caramori
Ian Adcock
Andrew J Halayko
Bernadett Tildy
Paolo Casolari
Kian Fan Chung
Karen Limbert Rempel
Alberto Papi
Mark M Perry
Journal: Respiratory Research (2018)
Discipline: CLINICAL MEDICINE
Keywords: Airway smooth muscle; COPD; CXCL8; Hydrogen sulfide; IL-6
Affiliations: School of Pharmacy & Biomedical Sciences, University of Portsmouth, St. Michael's Building, White Swan Road, Portsmouth, PO1 2DT, UK. ., Airways Disease, National Heart and Lung Institute, Imperial College, London & Royal Brompton NIHR Biomedical Research Unit, London, SW3 6LY, UK., Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate (CEMICEF, formerly termed Centro di Ricerca su Asma e BPCO), Università di Ferrara, Ferrara, Italy., Unità Operativa Complessa di Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università degli Studi di Messina, Messina, Italy., Departments of Internal Medicine & Physiology, Respiratory Hospital, Sherbrook Street, Winnipeg, MB, R3A 1R9, Canada.

Abstract:  Backbround: COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H2S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. Methods: We examined the effect of H2S upon ASM cells from COPD patients. ASM cells were isolated from non-smokers, smokers and patients with COPD (n = 9). Proliferation and cytokine release (IL-6 and CXCL8) of ASM was induced by FCS, and measured by bromodeoxyuridine incorporation and ELISA, respectively. Results: Exposure of ASM to H2S donors inhibited FCS-induced proliferation and cytokine release, but was less effective upon COPD ASM cells compared to the non-smokers and smokers. The mRNA and protein expression of the enzymes responsible for endogenous H2S production (cystathionine-β-synthase [CBS] and 3-mercaptopyruvate sulphur transferase [MPST]) were inhibited by H2S donors. Finally, we report that exogenous H2S inhibited FCS-stimulated phosphorylation of ERK-1/2 and p38 mitogen activated protein kinases (MAPKs), in the non-smoker and smoker ASM cells, with little effect in COPD cells. Conclusions: H2S production provides a novel mechanism for the repression of ASM proliferation and cytokine release. The ability of COPD ASM cells to respond to H2S is attenuated in COPD ASM cells despite the presence of the enzymes responsible for H2S production. 

Retracted: Yes

PubPeer comments:
 Figure 5A: A wetern blot (beta-actin, smokers), has been reused from another publication (O Leary L et al., 2016, FEBS Letters; Figure 3C, beta-actin). Unfortunately the samples are here presented as something very different. Figure 3A: The CBS blot (smokers) is too similar compared to the MPST blot (non smokers). ![file] ![file] , 
 I have contacted the lead author asking for them to send me the original figures so that we can respond to the query. I will be in touch when I get a response. BW, Ian , 
 #2 Dr. Adcock: Any update on this? , 
 Going through internal process as far as I am aware. Contact lead author for update. , 
 #4 Thank you for your reply. I directed my question to you as you had previously offered that you would be providing an update after you contacted the lead author. Did he not provide you with the original figures you requested? These types of concerns call into question the integrity of the data reported in this paper. , 
 I cannot comment on this whilst while an internal review is undertaken. I hope you understand. , 
 Retraction, 25 August 2021: https: respiratory-research.biomedcentral.com articles 10.1186 s12931-021-01816-7  The Editors-in-Chief have retracted this article. After publication concerns were raised about two of the figures, specifically: * In Figure 3a, the MPST blot for non-smokers appears to be the same as the CBS blot for smokers. * In Figure 5a, the beta-actin blot for smokers appears to be the same as the beta-actin blot for smokers in Figure 3c in a previous article [1]. An investigation by Imperial College into the integrity of these images was unable to reach a conclusion as it was established that the raw data and images from this study are not available for examination; it was therefore recommended that the article be retracted. Bernadett Tildy, Alberto Papi, Paolo Casolari, Gaetano Caramori, Karen Limbert Rempel, Andrew J. Halayko, Ian Adcock and Kian Fan Chung agree with this retraction. Mark Perry has not responded to correspondence from the Publisher about this retraction. , 
 I reached out to Dr Perry who was unable to provide the original figures as he did not keep the data after he left Imperial. According to College regulations he should have kept these for 10 years on file. We have been searching for these without success. ,