Endogenous production of hydrogen sulfide in human sinus mucosa and its expression levels are altered in patients with chronic rhinosinusitis with and without nasal polyps.
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNPs) or CRS without nasal polyps (CRSsNPs) is characterized by persistent inflammation of sinonasal mucosa. No one causative factor fully explains for the pathological manifestations of CRS. Endogenous hydrogen sulfide (H2S) has been shown to participate in inflammatory diseases, functioning as an inflammatory mediator in various organs. We analyzed the contents and synthesis activity of H2S, the expression and distribution pattern of H2S-generating enzymes, cystathione β-synthase (CBS), and cystathione γ-lyase (CSE) in CRSwNPs and CRSsNPs. The effects of H2S on the expression of CRS-relevant cytokines and the effects of cytokines on the expression of CBS and CSE were assessed in an in vitro experiment.


METHODS
The contents and synthesis activity of H2S and the expression and distribution pattern of CBS and CSE in sinus mucosa were evaluated using spectrophotometry, real-time polymerase chain reaction, Western blot, and immunohistochemistry. Cultured epithelial cells were used to elucidate the effects of H2S donor, sodium hydrosulfide (NaHS), on the expression of CRS-relevant cytokines and the effects of cytokines on H2S-generating enzymes expression.


RESULTS
The contents and synthesis activity of H2S were increased in CRSwNPs and CRSsNPs. CBS and CSE were localized to the superficial epithelium and submucosal glands, but CSE was also found in vascular endothelium. NaHS induced increased expression of IL-4, IL-5, interferon γ, and TNF-α. CBS and CSE expression in cultured cells was up-regulated by CRS-relevant cytokines.


CONCLUSIONS
H2S levels are increased in CRS, contributing to increased production of cytokines. These results suggest that H2S may function as inflammatory mediator in CRS.
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, South Korea.
Jae Woong
JW
Hwang
Young Joon
YJ
Jun
Se Jin
SJ
Park
Tae Hoon
TH
Kim
Ki Jeong
KJ
Lee
Soo Min
SM
Hwang
Seung Hoon
SH
Lee
Heung Man
HM
Lee
Sang Hag
SH
Lee
D000293:Adolescent; D000328:Adult; D019757:Carbon-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology*; D010256:Paranasal Sinuses / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D055815:Young Adult
D016207:Cytokines; D018836:Inflammation Mediators; C022696:O-succinylhomoserine (thiol)-lyase; D019757:Carbon-Oxygen Lyases; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide