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


OBJECTIVE
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.
Backus
Gillian S
GS
National Institute of Environmental Health Sciences, Laboratory of Respiratory Biology, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
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
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054426:Chemokine CXCL2 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D000393:Air Pollutants; D051940:B7-2 Antigen; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10; D010126:Ozone
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