Involvement of IL-10 in peroxisome proliferator-activated receptor gamma-mediated anti-inflammatory response in asthma.
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in controlling immune and inflammatory responses. Recent studies have demonstrated that activation of PPARgamma reduces airway hyper-responsiveness and activation of eosinophils that are increased by induction of asthma. We have used a mouse model of asthma to determine the role of PPARgamma in the regulation of the pulmonary immune response, more specifically in the involvement of immunoregulatory cytokine interleukin (IL)-10. Administration of PPARgamma agonists or adenovirus carrying PPARgamma cDNA (AdPPARgamma) reduced eosinophilic airway inflammation and airway hyper-responsiveness. Expression of PPARgamma was increased by ovalbumin inhalation, and the increase was further enhanced by the administration of PPARgamma agonists or AdPPARgamma. The increased IL-10 levels in lung tissues after ovalbumin inhalation were further increased by the administration of rosiglitazone, pioglitazone, or AdPPARgamma. Levels of IL-4, IL-5, and ovalbumin-specific IgE were also increased after ovalbumin inhalation, and the increased levels were significantly reduced by the administration of the PPARgamma agonists or AdPPARgamma. The results also showed that inhibition of IL-10 activity with anti-IL-10 receptor antibody partially restored the inflammation. These findings suggest that a protective role of PPARgamma in the pathogenesis of the asthma is partly mediated through an IL-10-dependent mechanism.
Kim
So Ri
SR
Department of Internal Medicine, Airway Remodeling Laboratory, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, 634-18, Keumamdong, Jeonju, 561-712, South Korea.
Lee
Kyung Sun
KS
Park
Hee Sun
HS
Park
Seoung Ju
SJ
Min
Kyung Hoon
KH
Jin
Sun Mi
SM
Lee
Yong Chul
YC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D007073:Immunoglobulin E / Q000032:analysis; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000032:analysis* / Q000502:physiology; D007378:Interleukins / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000473:pathology; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000494:pharmacology / Q000502:physiology*; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D007378:Interleukins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016753:Interleukin-10; D007073:Immunoglobulin E; D000077205:Pioglitazone