IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung

Autor:	Ole Henning Skjønsberg, Vigdis Hillestad, Fadila Telarevic Cero, Else Marit Løberg, Geir Christensen, Karl-Otto Larsen
Rok vydání:	2012
Předmět:	Male Pulmonary and Respiratory Medicine T-Lymphocytes medicine.medical_treatment Clinical Biochemistry Apoptosis Inflammation Biology Matrix metalloproteinase Gene Expression Regulation Enzymologic Mice Matrix Metalloproteinase 12 medicine Animals RNA Messenger Lung Molecular Biology Cathepsin Receptors Interleukin-18 Interleukin-18 Receptors Interleukin-12 Interleukin Drug Synergism Cathepsins Interleukin-12 Recombinant Proteins Up-Regulation Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cytokine Immunology Cancer research CXCL9 Drug Therapy Combination Tumor necrosis factor alpha medicine.symptom
Zdroj:	Experimental Lung Research. 38:406-419
ISSN:	1521-0499 0190-2148
DOI:	10.3109/01902148.2012.716903
Popis:	Interleukin (IL)-18 is a pro-inflammatory cytokine suggested to be involved in the development of pulmonary emphysema and inflammation. Studies involving immunology and cancer have revealed that IL-18 can have synergistic effects with IL-12. We have studied the presence of IL-18 and IL-12 receptors (IL-18R/IL-12R) in the lungs and whether IL-18 and IL-12, alone or in combination, have the ability to initiate the induction of mediators related to the development of emphysema and inflammation. The expression of the IL-18R was abundant in lungs compared to other organs (heart, liver, and spleen), and the IL-12R was also expressed in lung tissue. Mice treated with i.p. injection of recombinant murine IL-18 or IL-12 expressed significantly higher pulmonary mRNA levels of the matrix degrading enzymes metalloproteinase (MMP) 12 and cathepsin S, in addition to interferon-γ, tumor necrosis factor-α, and CXC chemokine ligand 9 (CXCL9) (all P < .05) than controls (received PBS). Treatment with IL-18 and IL-12 in combination showed an even more pronounced induction of these mediators, as well as a significant increase in MMP-9, IL-6, IL-1β, and transforming growth factor-β (P < .05). Furthermore, cellular apoptosis in lung tissue was induced. Immunohistochemical analysis revealed T-cell infiltration in pulmonary vessels following co-stimulation. In summary, IL-18 and IL-12 exert a synergistic effect on the lungs by inducing MMPs, cathepsins S, and pro-inflammatory cytokines, which may promote pulmonary emphysema and inflammation. The synergy between IL-18 and IL-12 involves infiltration of T-cells in the lungs, possibly induced by the T-cell chemoattractant CXCL9.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::349314a512f8ba93a20cfd9160c84e9d https://doi.org/10.3109/01902148.2012.716903 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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