Anti-Inflammatory Effect of Sulfur Dioxide and Sulfite on Cigarette Smoke Exposed Human Airway Smooth Muscle Cells

Sulfur dioxide is an endogenously produced gas, once thought to be solely toxic. More recent studies have demonstrated that at physiological concentrations however it can also have beneficial effects, such as inhibition of inflammation, vasodilation, and relaxation of smooth muscle. Airway smooth muscle cells (HASMC) are involved in multiple aspects of chronic inflammatory airway diseases such as asthma and COPD, including airflow restriction and release of pro-inflammatory mediators. While the response of HASMC to cigarette smoke exposure has been studied, the effects of sulfur dioxide on the cigarette smoke-induced inflammatory mediators have not. It has been proposed that sulfur dioxide creates a hypoxic state, similar to cigarette smoke, which suggested that the hypoxia inducible factor-1α (HIF-1α) may be involved in mediating the resulting inflammation. This also suggested that the effects of cigarette smoke and sulfur dioxide, two air pollutants commonly present in the industrial areas south of Houston, might be cumulative. This led us to hypothesize that co-exposure to cigarette smoke and sulfur dioxide would antagonize the cigarette smoke-induced inflammation and that HIF-1α would mediate the inflammatory response by its effects on the MAPK and NF-κB pathways. Although sulfur dioxide has been shown to induce inflammation and airway smooth muscle constriction, these effects primarily occur at higher concentration. The exception to this is a group of individuals with severe asthma, COPD or a sensitivity to sulfur dioxide that react negatively to low concentrations of sulfur dioxide (< 1 ppm). These individuals typically have elevated levels of pro-inflammatory cytokines and we have found that exposure of inflammatory cytokine-stimulated HASMC to sulfur dioxide does result in augmented release of GM-CSF, a pro-inflammatory cytokine that has been increasingly recognized as a major regulator of airway inflammation. However, we also found that sulfur dioxide reduced cigarette smoke-induced GM-CSF release from HASMC via down-regulation of the p38, p44/42 and NF-κB pathways. While HIF-1α activity clearly limits the NF-κB-driven induction of GM-CSF, it does not appear that sulfur dioxide is reducing GM-CSF through a HIF-1α mediated mechanism.

Name thesis:degree_name

Biochemistry and Molecular Biology (Doctoral)

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Rolls, Barbara Ann

• mitogen‐activated protein kinase (MAPK)
• p38 MAPK
• NF‐kappaB (NF‐KB)
• GM-CSF
• cigarette smoke
• sulfite
• sulfur dioxide
• hypoxia‐inducible factor (HIF)
• inflammation
• airway smooth muscle

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/11336

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/11336