Skip to main content
SpringerLink
Log in

H2S and Inflammation: An Overview

  • Chapter
Book cover Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 230))

Abstract

Inflammation is a response to traumatic, infectious, post-ischemic, toxic, or autoimmune injury. However, uncontrolled inflammation can lead to disease, and inflammation is now believed to be responsible for several disease conditions. Research in our laboratory has shown that hydrogen sulfide (H2S) acts as a novel mediator of inflammation. At present, work in several research groups worldwide is focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions. Most of this research involved working with animal models of disease and in vitro systems. Recent research, however, points to a role of H2S in clinical inflammatory disease as well. This chapter describes our current understanding of the role of H2S in inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ang SF, Moochhala S, Bhatia M (2010) Hydrogen sulfide promotes transient receptor potential vanilloid 1-mediated neurogenic inflammation in polymicrobial sepsis. Crit Care Med 38:619–628

    Article  CAS  PubMed  Google Scholar 

  • Ang SF, Moochhala SM, MacAry PA, Bhatia M (2011a) Hydrogen sulfide and neurogenic inflammation in polymicrobial sepsis: involvement of substance P and ERK-NF-κB signaling. PLoS ONE 6, e24535

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ang SF, Sio SW, Moochhala SM, MacAry PA, Bhatia M (2011b) Hydrogen sulfide upregulates cyclooxygenase-2 and prostaglandin E metabolite in sepsis-evoked acute lung injury via transient receptor potential vanilloid type 1 channel activation. J Immunol 187:4778–4787

    Article  CAS  PubMed  Google Scholar 

  • Ang AD, Rivers-Auty J, Hegde A, Ishii I, Bhatia M (2013) The effect of CSE gene deletion in caerulein-induced acute pancreatitis in the mouse. Am J Physiol Gastrointest Liver Physiol 305:G712–G721

    Article  CAS  PubMed  Google Scholar 

  • Badiei A, Rivers-Auty J, Ang AD, Bhatia M (2013) Inhibition of hydrogen sulfide production by gene silencing attenuates inflammatory activity of LPS-activated RAW 264.7 cells. Appl Microbiol Biotechnol 97:7845–7852

    Article  CAS  PubMed  Google Scholar 

  • Bhatia M (2010) Hydrogen sulfide and substance P in inflammation. Antioxid Redox Signal 12:1191–1202

    Article  CAS  PubMed  Google Scholar 

  • Bhatia M (2012) Role of hydrogen sulfide in the pathology of inflammation. Scientifica 2012, 159680

    Article  PubMed Central  PubMed  Google Scholar 

  • Bhatia M, Moochhala S (2004) Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 202:145–156

    Article  CAS  PubMed  Google Scholar 

  • Bhatia M, Brady M, Shokuhi S, Christmas SE, Neoptolemos JP, Slavin J (2000) Inflammatory mediators in acute pancreatitis. J Pathol 190:117–125

    Article  CAS  PubMed  Google Scholar 

  • Bhatia M, Wong FL, Fu D, Lau HY, Moochhala S, Moore PK (2005a) Role of hydrogen sulfide in acute pancreatitis and associated lung injury. FASEB J 19:623–625

    CAS  PubMed  Google Scholar 

  • Bhatia M, Sidhapuriwala J, Moochhala S, Moore PK (2005b) Hydrogen sulphide is a mediator of carrageenan-induced hindpaw oedema in the rat. Br J Pharmacol 145:141–144

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, Chevali L (2005c) Pathophysiology of acute pancreatitis. Pancreatology 5:132–144

    Article  PubMed  Google Scholar 

  • Bhatia M, Zhi L, Zhang H, Ng SW, Moore PK (2006) Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice. Am J Physiol Lung Cell Mol Physiol 291:L896–L904

    Article  CAS  PubMed  Google Scholar 

  • Bhatia M, Sidhapuriwala J, Sparatore A, Moore PK (2008a) Treatment with H2S-releasing diclofenac protects mice against acute pancreatitis-associated lung injury. Shock 29:84–88

    CAS  PubMed  Google Scholar 

  • Bhatia M, Sidhapuriwala J, Ng SW, Tamizhselvi R, Moochhala S (2008b) Proinflammatory effects of hydrogen sulfide on substance P in caerulein-induced acute pancreatitis. J Cell Mol Med 12:580–590

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bhatia M, He M, Zhang H, Moochhala S (2009) Sepsis as a model of SIRS. Front Biosci [Animals in SIRS Research editor Bhatia M (a Special issue of encyclopedia of bioscience, published by frontiers in bioscience)] 14:4703–4711

    Google Scholar 

  • Chen YH, Yao WZ, Geng B, Ding YL, Lu M, Zhao MW, Tang CS (2005) Endogenous hydrogen sulfide in patients with COPD. Chest 128:3205–3211

    Article  CAS  PubMed  Google Scholar 

  • Church D, Elsayed S, Reid O, Winston B, Lindsay R (2006) Burn wound infections. Clin Microbiol Rev 19:403–434

    Article  PubMed Central  PubMed  Google Scholar 

  • Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Módis K, Panopoulos P, Asimakopoulou A, Gerö D, Sharina I, Martin E, Szabo C (2012) Proc Natl Acad Sci U S A 109:9161–9166

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Collin M, Anuar F, Murch O, Bhatia M, Moore PK, Thiemermann C (2005) Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmacol 146:498–505

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Decramer M, Janssens W, Miravitlles M (2012) Chronic obstructive pulmonary disease. Lancet 379:1341–1351

    Article  PubMed  Google Scholar 

  • Endorf FW, Ahrenholz D (2011) Burn management. Curr Opin Crit Care 17:601–605

    Article  PubMed  Google Scholar 

  • Fiorucci S, Orlandi S, Mencarelli A, Caliendo G, Santagada V, Distrutti E, Santucci L, Cirino G, Wallace JL (2007) Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis. Br J Pharmacol 150:996–1002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fox B, Schantz JT, Haigh R, Wood ME, Moore PK, Viner N, Spencer JP, Winyard PG, Whiteman M (2012) Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H2S a novel cytoprotective mediator in the inflamed joint? J Cell Mol Med 16:896–910

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hegde A, Bhatia M (2011) Hydrogen sulfide in inflammation: friend or foe? Inflamm Allergy Drug Targets 10:118–122

    Article  CAS  PubMed  Google Scholar 

  • Kloesch B, Liszt M, Krehan D, Broell J, Kiener H, Steiner G (2012) High concentrations of hydrogen sulphide elevate the expression of a series of pro-inflammatory genes in fibroblast-like synoviocytes derived from rheumatoid and osteoarthritis patients. Immunol Lett 141:197–203

    Article  CAS  PubMed  Google Scholar 

  • Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC (2010) The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 38:367–374

    Article  PubMed  Google Scholar 

  • Li L, Bhatia M, Zhu YZ, Ramnath RD, Wang ZJ, Anuar F, Whiteman M, Salto-Tellez M, Moore PK (2005) Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J 19:1196–1198

    CAS  PubMed  Google Scholar 

  • Li L, Rossoni G, Sparatore A, Lee LC, Del Soldato P, Moore PK (2007) Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic Biol Med 42:706–719

    Article  PubMed  Google Scholar 

  • Li L, Salto-Tellez M, Tan CH, Whiteman M, Moore PK (2009) GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat. Free Radic Biol Med 47:103–113

    Article  CAS  PubMed  Google Scholar 

  • Li L, Rose P, Moore PK (2011) Hydrogen sulfide and cell signaling. Annu Rev Pharmacol Toxicol 51:169–187

    Article  CAS  PubMed  Google Scholar 

  • Li L, Fox B, Keeble J, Salto-Tellez M, Winyard PG, Wood ME, Moore PK, Whiteman M (2013) The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells. J Cell Mol Med 17:365–376

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ma VY, Chan L, Carruthers KJ (2014) Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil 95:986–995

    Article  PubMed Central  PubMed  Google Scholar 

  • Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554

    Article  PubMed  Google Scholar 

  • Mazumder B, Li X, Barik S (2010) Translation control: a multifaceted regulator of inflammatory response. J Immunol 184:3311–3319

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Moore PK, Bhatia M, Moochhala S (2003) Hydrogen sulphide: from the smell of the past to the mediator of the future? Trends Pharmacol Sci 24:609–611

    Article  CAS  PubMed  Google Scholar 

  • Nathan C (2002) Points of control in inflammation. Nature 420:846–852

    Article  CAS  PubMed  Google Scholar 

  • Norris EJ, Feilen N, Nguyen NH, Culberson CR, Shin MC, Fish M, Clemens MG (2013) Hydrogen sulfide modulates sinusoidal constriction and contributes to hepatic microcirculatory dysfunction during endotoxemia. Am J Physiol Gastrointest Liver Physiol 304:G1070–G1078

    Article  CAS  PubMed  Google Scholar 

  • Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, Gangarosa LM, Thiny MT, Stizenberg K, Morgan DR, Ringel Y, Kim HP, Dibonaventura MD, Carroll CF, Allen JK, Cook SF, Sandler RS, Kappelman MD, Shaheen NJ (2012) Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 143:1179–1187

    Article  PubMed Central  PubMed  Google Scholar 

  • Polytarchou C, Koukos G, Iliopoulos D (2014) Systems biology in inflammatory bowel diseases: ready for prime time. Curr Opin Gastroenterol 30(4):339–346

    Article  CAS  PubMed  Google Scholar 

  • Ramnath RD, Ng SW, He M, Sun J, Zhang H, Bawa MS, Bhatia M (2006) Inflammatory mediators in sepsis: cytokines, chemokines, adhesion molecules, and gases. J Organ Dysfunct 2:80–92

    Article  Google Scholar 

  • Shanmugam MK, Jing Z, Bhatia M (2009) Aminooxyacetate inhibits hydrogen sulfide and ammonium synthesis and protects mice in acute pancreatitis. Int J Integr Biol 8:7–14

    CAS  Google Scholar 

  • Sidhapuriwala J, Li L, Sparatore A, Bhatia M, Moore PK (2007) Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat. Eur J Pharmacol 569:149–154

    Article  CAS  PubMed  Google Scholar 

  • Sidhapuriwala J, Hegde A, Ang AD, Zhu YZ, Bhatia M (2012) Effects of S-propargyl-cysteine (SPRC) in caerulein-induced acute pancreatitis in mice. PLoS ONE 7, e32574

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sun Y, Wang XM, Chen YH, Zhu RX, Liao CC (2013) Exhaled hydrogen sulfide in patients with chronic obstructive pulmonary disease and its correlation with exhaled nitric oxide. Chin Med J (Engl) 126:3240–3244

    CAS  Google Scholar 

  • Tamizhselvi R, Moore PK, Bhatia M (2007) Hydrogen sulfide acts as a mediator of inflammation in acute pancreatitis: in vitro studies using isolated mouse pancreatic acinar cells. J Cell Mol Med 11:315–326

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tamizhselvi R, Moore PK, Bhatia M (2008) Inhibition of hydrogen sulfide synthesis attenuates chemokine production and protects mice against acute pancreatitis and associated lung injury. Pancreas 36:e24–e31

    Article  CAS  PubMed  Google Scholar 

  • Tamizhselvi R, Sun J, Hua KY, Bhatia M (2009) Effect of hydrogen sulfide on PI3K-AKT pathway and on caerulein- induced cytokine production in isolated mouse pancreatic acinar cells. J Pharmacol Exp Ther 329:1166–1177

    Article  CAS  PubMed  Google Scholar 

  • Tamizhselvi R, Koh YH, Sun J, Zhang H, Bhatia M (2010) Hydrogen sulfide-induces ICAM-1 expression and neutrophil adhesion to caerulein treated pancreatic acinar cells through NF-κB and Src-family kinases pathway. Exp Cell Res 316:1625–1636

    Article  CAS  PubMed  Google Scholar 

  • Tamizhselvi R, Shrivastava P, Koh YH, Zhang H, Bhatia M (2011) Preprotachykinin-A gene deletion regulates hydrogen sulfide induced toll-like receptor 4 signaling pathway in cerulein-treated pancreatic acinar cells. Pancreas 40:444–452

    Article  CAS  PubMed  Google Scholar 

  • Wang R (2012) Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev 92:791–896

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Guo Z, Wang S (2014) The binding site for the transcription factor, NF-κB, on the cystathionine γ-lyase promoter is critical for LPS-induced cystathionine γ-lyase expression. Int J Mol Med 34(2):639–645

    PubMed  Google Scholar 

  • Yan Y, Chen C, Zhou H, Gao H, Chen L, Chen L, Gao L, Zhao R, Sun Y (2013) Endogenous hydrogen sulfide formation mediates the liver damage in endotoxemic rats. Res Vet Sci 94:590–595

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Zhi L, Moore PK, Bhatia M (2006) The role of hydrogen sulfide in cecal ligation and puncture induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol 290:L1193–L1201

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Zhi L, Moochhala S, Moore PK, Bhatia M (2007a) Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture induced sepsis in mice by up-regulating the production of cytokines and chemokines via NF-κB. Am J Physiol Lung Cell Mol Physiol 292:L960–L971

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Zhi L, Moochhala S, Moore PK, Bhatia M (2007b) Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture induced sepsis. J Leukoc Biol 82:894–905

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Hegde A, Ng SW, Adhikari S, Moochhala SM, Bhatia M (2007c) Hydrogen sulfide up-regulates substance P in polymicrobial sepsis associated Lung Injury. J Immunol 179:4153–4160

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Moochhala S, Bhatia M (2008) Endogenous hydrogen sulfide regulates inflammatory response by activating the extracellular signal-regulated kinase (ERK) pathway in polymicrobial sepsis. J Immunol 181:4320–4331

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Sio SW, Moochhala S, Bhatia M (2010) Role of hydrogen sulfide in severe burn injury-induced inflammation in the mouse. Mol Med 16:417–424

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhi L, Ang AD, Zhang H, Moore PK, Bhatia M (2007) Hydrogen sulfide induces the synthesis of pro-inflammatory cytokines in human monocyte cell line U937 via ERK-NFκB pathway. J Leukoc Biol 81:1322–1332

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author’s laboratory is supported by research grants from the Lottery Health, Arthritis New Zealand, Maurice and Phyllis Paykel Trust, and University of Otago (Establishment Grant and University of Otago Research Grant).

Author information

Authors and Affiliations

  1. Department of Pathology, University of Otago, Christchurch, 2 Riccarton Avenue, 4345, Christchurch, 8140, New Zealand

    Madhav Bhatia

Authors
  1. Madhav Bhatia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Madhav Bhatia .

Editor information

Editors and Affiliations

  1. National University of Singapore, Singapore, Singapore

    Philip K. Moore

  2. ST. Luke's Campus, University of Exeter Medical School, Exeter, United Kingdom

    Matt Whiteman

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bhatia, M. (2015). H2S and Inflammation: An Overview. In: Moore, P., Whiteman, M. (eds) Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide. Handbook of Experimental Pharmacology, vol 230. Springer, Cham. https://doi.org/10.1007/978-3-319-18144-8_8

Download citation

Publish with us

Policies and ethics

Search

Navigation