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TNF and IL-6 mediate MIP-1alpha expression in bleomycin-induced lung injury.
J Leukoc Biol. 1998 Oct; 64(4):528-36.JL

Abstract

Previously, macrophage inflammatory protein-1alpha (MIP-1alpha), a member of the C-C chemokine family, has been implicated in bleomycin-induced pulmonary fibrosis, a model of the human disease idiopathic pulmonary fibrosis. Neutralization of MIP-1alpha protein with anti-MIP-1alpha antibodies significantly attenuated both mononuclear phagocyte recruitment and pulmonary fibrosis in bleomycin-challenged CBA/J mice. However, the specific stimuli for MIP-1alpha expression in the bleomycin-induced lesion have not been characterized. In this report, two mediators of the inflammatory response to bleomycin, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were evaluated as putative stimuli for MIP-1alpha expression after bleomycin challenge in CBA/J mice. Elevated levels of bioactive TNF and IL-6 were detected in bronchoalveolar lavage (BAL) fluid and lung homogenates from bleomycin-treated CBA/J mice at time points post-bleomycin challenge, which precede MIP-1alpha protein expression. Treatment of bleomycin-challenged mice with soluble TNF receptor (sTNFr) or anti-IL-6 antibodies significantly decreased MIP-1alpha protein expression in the lungs. Furthermore, normal alveolar macrophages secreted elevated levels of MIP-1alpha protein in response to treatment with TNF plus IL-6 or bleomycin plus IL-6, but not TNF, bleomycin, or IL-6 alone. Finally, leukocytes recovered from the BAL fluid of bleomycin-challenged mice secreted higher levels of MIP-1alpha protein, compared to controls, when treated with TNF alone. Based on the data presented here, we propose that TNF and IL-6 are part of a cytokine network that modulates MIP-1alpha protein expression in the profibrotic inflammatory lesion during the response to intratracheal bleomycin challenge.

Authors+Show Affiliations

Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9766634

Citation

Smith, R E., et al. "TNF and IL-6 Mediate MIP-1alpha Expression in Bleomycin-induced Lung Injury." Journal of Leukocyte Biology, vol. 64, no. 4, 1998, pp. 528-36.
Smith RE, Strieter RM, Phan SH, et al. TNF and IL-6 mediate MIP-1alpha expression in bleomycin-induced lung injury. J Leukoc Biol. 1998;64(4):528-36.
Smith, R. E., Strieter, R. M., Phan, S. H., Lukacs, N., & Kunkel, S. L. (1998). TNF and IL-6 mediate MIP-1alpha expression in bleomycin-induced lung injury. Journal of Leukocyte Biology, 64(4), 528-36.
Smith RE, et al. TNF and IL-6 Mediate MIP-1alpha Expression in Bleomycin-induced Lung Injury. J Leukoc Biol. 1998;64(4):528-36. PubMed PMID: 9766634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF and IL-6 mediate MIP-1alpha expression in bleomycin-induced lung injury. AU - Smith,R E, AU - Strieter,R M, AU - Phan,S H, AU - Lukacs,N, AU - Kunkel,S L, PY - 1998/10/10/pubmed PY - 1998/10/10/medline PY - 1998/10/10/entrez SP - 528 EP - 36 JF - Journal of leukocyte biology JO - J Leukoc Biol VL - 64 IS - 4 N2 - Previously, macrophage inflammatory protein-1alpha (MIP-1alpha), a member of the C-C chemokine family, has been implicated in bleomycin-induced pulmonary fibrosis, a model of the human disease idiopathic pulmonary fibrosis. Neutralization of MIP-1alpha protein with anti-MIP-1alpha antibodies significantly attenuated both mononuclear phagocyte recruitment and pulmonary fibrosis in bleomycin-challenged CBA/J mice. However, the specific stimuli for MIP-1alpha expression in the bleomycin-induced lesion have not been characterized. In this report, two mediators of the inflammatory response to bleomycin, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were evaluated as putative stimuli for MIP-1alpha expression after bleomycin challenge in CBA/J mice. Elevated levels of bioactive TNF and IL-6 were detected in bronchoalveolar lavage (BAL) fluid and lung homogenates from bleomycin-treated CBA/J mice at time points post-bleomycin challenge, which precede MIP-1alpha protein expression. Treatment of bleomycin-challenged mice with soluble TNF receptor (sTNFr) or anti-IL-6 antibodies significantly decreased MIP-1alpha protein expression in the lungs. Furthermore, normal alveolar macrophages secreted elevated levels of MIP-1alpha protein in response to treatment with TNF plus IL-6 or bleomycin plus IL-6, but not TNF, bleomycin, or IL-6 alone. Finally, leukocytes recovered from the BAL fluid of bleomycin-challenged mice secreted higher levels of MIP-1alpha protein, compared to controls, when treated with TNF alone. Based on the data presented here, we propose that TNF and IL-6 are part of a cytokine network that modulates MIP-1alpha protein expression in the profibrotic inflammatory lesion during the response to intratracheal bleomycin challenge. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/9766634/TNF_and_IL_6_mediate_MIP_1alpha_expression_in_bleomycin_induced_lung_injury_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0741-5400&date=1998&volume=64&issue=4&spage=528 DB - PRIME DP - Unbound Medicine ER -