Am. J. Respir. Cell Mol. Biol., Volume 25, Number 5, November, 2001 592-599

Normal Human Lung Fibroblasts Differently Modulate Interleukin-10 and Interleukin-12 Production by Monocytes
Implications for an Altered Immune Response in Pulmonary Chronic Inflammation

Carlo Vancheri, Claudio Mastruzzo, Valerio Tomaselli, Maria Angela Sortino, Leda D'Amico, Guglielmo Bellistrí, Maria P. Pistorio, Elisa Trovato Salinaro, Filippo Palermo, Antonino Mistretta, and Nunzio Crimi

Institutes of Respiratory and Infectious Diseases and Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy

The ability of lung fibroblasts to modulate the immune response has been evaluated by analyzing the synthesis and release of interleukin (IL)-10 and IL-12 by lipopolysaccharide (LPS)-stimulated peripheral blood monocytes exposed to pulmonary fibroblast conditioned medium (FCM). IL-10 and IL-12 contents and gene expression were markedly modified by treatment with FCM as measured by ELISA (+97.5 ± 12.8% and -68 ± 7.3% for IL-10 and IL-12, respectively), immunocytochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR). These effects appeared to be mediated by prostaglandin E₂ (PGE₂) as the modified release of both cytokines was reduced by treatment with indomethacin and mimicked by addition of exogenous PGE_2. As a result of the enhanced production of IL-10, exposure of LPS/interferon (IFN)--activated monocytes to FCM was also able to reduce the expression of the class II major histocompatibility complex (MHC) molecule, human leukocyte-associated antigen-DR (HLA-DR) (51.8 ± 8.7%) and of the costimulatory molecule, CD40 (53.9 ± 11.7%). The expression of both molecules was completely restored when monocytes were pretreated with a neutralizing anti-IL-10 monoclonal antibody. The FCM obtained from fibrotic lung fibroblasts was instead less efficacious in potentiating LPS-stimulated IL-10 release and, consequently, in reducing HLA-DR and CD40 expression, suggesting that an impairment of the immune regulation operated by fibroblasts may be involved in the maintenance of chronic pulmonary inflammation.

This article has been cited by other articles:

				M. G. Haase, A. Klawitter, P. Geyer, and G. B. Baretton Expression of the Immunomodulator IL-10 in Type I Pneumocytes of the Rat: Alterations of IL-10 Expression in Radiation-induced Lung Damage J. Histochem. Cytochem., November 1, 2007; 55(11): 1167 - 1172. [Abstract] [Full Text] [PDF]

				P. E. Thomas, M. Peters-Golden, E. S. White, V. J. Thannickal, and B. B. Moore PGE2 inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L417 - L428. [Abstract] [Full Text] [PDF]

				M. Booth, J. K. Mwatha, S. Joseph, F. M. Jones, H. Kadzo, E. Ireri, F. Kazibwe, J. Kemijumbi, C. Kariuki, G. Kimani, et al. Periportal Fibrosis in Human Schistosoma mansoni Infection Is Associated with Low IL-10, Low IFN-{gamma}, High TNF-{alpha}, or Low RANTES, Depending on Age and Gender J. Immunol., January 15, 2004; 172(2): 1295 - 1303. [Abstract] [Full Text] [PDF]

				P.G. Tsoutsou and K.I. Gourgoulianis Role of interleukin-10 in idiopathic pulmonary fibrosis Eur. Respir. J., January 1, 2004; 23(1): 179 - 180. [Full Text] [PDF]

				N. Heuze-Vourc'h, L. Zhu, K. Krysan, R. K. Batra, S. Sharma, and S. M. Dubinett Abnormal Interleukin 10R{alpha} Expression Contributes to the Maintenance of Elevated Cyclooxygenase-2 in Non-Small Cell Lung Cancer Cells Cancer Res., February 15, 2003; 63(4): 766 - 770. [Abstract] [Full Text] [PDF]