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Protective role of interleukin-10 in Ozone-induced pulmonary inflammation**
Citation:
Backus, G., R. Howden, J. Fostel, A. Bauer, H. Cho, J. Marzec, D. Peden, AND S. Kleeberger. Protective role of interleukin-10 in Ozone-induced pulmonary inflammation**. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 118(12):1721-7, (2011).
Impact/Purpose:
This manuscript was approved via paper file EPHD-12-051 and was entered into the Science Inventory
Description:
Background: The mechanisms underlying ozone (03)-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 03-induced pulmonary inflammation in mice. Methods: 1110-deficient (1110-/-) and wild-type (1110+/+) mice were exposed to 0.3 ppm 03 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 03-induced inflammation. Results: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in 1110-/mice than in I110+/+ mice after exposure to 03 at all time points tested. 03-enhanced nuclear NF-KB translocation was elevated in the lungs of III 0-/-compared with III 0+/+ mice. Gene expression analyses revealed several IL-10-dependent and 03-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3. Conclusions: Results indicate that IL-10 protects against 03-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 03-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals