摘要：Background The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives We investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O3-induced pulmonary inflammation in mice. Methods Il10 -deficient ( Il10 −/−) and wild-type ( Il10 +/+) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. Results Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10 −/− mice than in Il10 +/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10 −/− compared with Il10 +/+ mice. Gene expression analyses revealed several IL-10–dependent and O3-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3. Conclusions Results indicate that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
