Is hydrogen sulfide a novel endogenous anti-inflammatory mediator? (360G-Wellcome-091725_Z_10_Z)

£143,094

The gaseous mediator hydrogen sulfide (H2S), formed via the enzyme cystathionine-gamma-lyase (CSE), has been proposed as a novel mediator of inflammation. However, the precise role of H2S (and CSE) in the inflammatory process have yet to be investigated. We propose that in the inflamed human joint, increased expression and activity of CSE in cultured human fibroblast-like synoviocytes (HLFS) increases synovial H2S levels as a novel endogenous anti-inflammatory response to pro-inflammatory mediat ors. Our previous work supports this hypothesis since (i) H2S levels were markedly increased in synovial fluid (SF) aspirates from patients with chronic inflammatory joint diseases and in adjuvant-treated rats compared to matched blood and non-inflammatory SF controls. Furthermore SF H2S levels correlated with clinical indices of inflammation, (ii) CSE expression and activity were induced by several pro-inflammatory mediators (i.e. LPS, IL-1beta,IL-6,TNF-alpha) and (iii) slow generation of H2S u sing a novel infusion technique or our H2S generating molecule GYY4137 inhibited the synthesis of pro-inflammatory mediators. Using cultured HLFS we propose to investigate the mechanisms by which (a) endogenous (CSE-derived) H2S and (b) exogenous (pharmacological) H2S is anti-inflammatory. This project will provide the scientific groundwork for the development of novel therapeutic approaches to chronic inflammatory disorders including rheumatoid arthritis.

Where is this data from?

This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.

Grant Details

Amount Awarded 143094
Applicant Surname Whiteman
Approval Committee Physiological Sciences Funding Committee
Award Date 2010-07-06T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Project Grant
Internal ID 091725/Z/10/Z
Lead Applicant Prof Matt Whiteman
Other Applicant(s) Dr Mark Wood, Prof Paul Winyard
Partnership Value 143094
Planned Dates: End Date 2013-10-10T00:00:00+00:00
Planned Dates: Start Date 2010-10-11T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South West