An anti-inflammatory role for carbon monoxide and heme oxygenase-1 in chronic Th2-mediated murine colitis

Shehzad Z. Sheikh, Refaat A. Hegazi, Taku Kobayashi, Joseph C. Onyiah, Steven M. Russo, Katsuyoshi Matsuoka, Antonia R. Sepulveda, Fengling Li, Leo E. Otterbein, Scott E. Plevy

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)


Cigarette smoking is a significant environmental factor in the human inflammatory bowel diseases, remarkably, conferring protection in ulcerative colitis. We previously demonstrated that a prominent component of cigarette smoke, CO, suppresses Th17-mediated experimental colitis in IL-10-/- mice through a heme oxygenase (HO)-1-dependent pathway. In this study, homeostatic and therapeutic effects of CO and HO-1 were determined in chronic colonic inflammation in TCR-α-deficient (-/-) mice, in which colitis is mediated by Th2 cytokines, similar to the cytokine milieu described in human ulcerative colitis. TCRα-/- mice exposed to CO or treated with the pharmacologic HO-1 inducer cobalt protoporphyrin demonstrated amelioration of active colitis. CO and cobalt protoporphyrin suppressed colonic IL-1β, TNF, and IL-4 production, whereas IL-10 protein secretion was increased. CO induced IL-10 expression in macrophages and in vivo through an HO-1-dependent pathway. Bacterial products regulate HO-1 expression in macrophages through MyD88- and IL-10-dependent pathways. CO exposure and pharmacologic HO-1 induction in vivo resulted in increased expression of HO-1 and IL-10 in CD11b+ lamina propria mononuclear cells. Moreover, induction of the IL-10 family member IL-22 was demonstrated in CD11b- lamina propria mononuclear cells. In conclusion, CO and HO-1 induction ameliorated active colitis in TCRβ-/- mice, and therapeutic effects correlated with induction of IL-10. This study provides further evidence that HO-1 mediates an important homeostatic pathway with pleiotropic anti-inflammatory effects in different experimental models of colitis and that targeting HO-1, therefore, is a potential therapeutic strategy in human inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)5506-5513
Number of pages8
JournalJournal of Immunology
Issue number9
Publication statusPublished - 2011 May 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'An anti-inflammatory role for carbon monoxide and heme oxygenase-1 in chronic Th2-mediated murine colitis'. Together they form a unique fingerprint.

Cite this