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Protective Role of IL-10 in Ozone-induced Pulmonary Inflammation

ABSTRACT: Background: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: The current study investigated the molecular mechanisms underlying 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 following 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 utilized global mRNA expression analyses of lung tissue with Ingenuity Pathway Analyses (IPA) 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-kB translocation was elevated in the lungs of Il10-/- compared to Il10+/+ mice. Gene expression analyses revealed several key IL-10 and O3-dependent mediators, including IL-6, MIP-2, IL-1 and CD86. Conclusions: Results indicated that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several novel genetic targets (e.g. Ccr1, Socs3, Il33, Hat1, and Gale) through which IL10 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. PARALLEL study design with 26 samples. Biological replicates: 2 to 3 replicates per group with wild type air exposed animals as controls for each time point (24, 48, 72 hours). Time-Course, Dose-Response, Strain comparison


ORGANISM(S): Mus musculus  

SUBMITTER: Steve R Kleeberger   Hye-Youn Cho  R Howden  Gillian S Backus  Jacqueline Marzec  Steven R Kleeberger  A K Bauer  Jennifer Fostel  D B Peden 

PROVIDER: E-GEOD-25095 | ArrayExpress | 2011-10-18



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Protective role of interleukin-10 in ozone-induced pulmonary inflammation.

Backus Gillian S GS   Howden Reuben R   Fostel Jennifer J   Bauer Alison K AK   Cho Hye-Youn HY   Marzec Jacqui J   Peden David B DB   Kleeberger Steven R SR  

Environmental health perspectives 20100908 12

<h4>Background</h4>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.<h4>Objectives</h4>We investigated the molecular mechanisms underlying interleuken-10 (IL-10)-mediated attenuation of O₃-induced pulmonary inflammation in mice.<h4>Methods</h4>Il10-deficient (Il10(-/-)) and wild-type (Il10(+/+)) mice were exposed to 0.3 ppm O₃ or filtered air for 24, 48, or 7  ...[more]

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