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Nickel alterations of TLR2-dependent chemokine profiles in lung fibroblasts are mediated by COX-2.
Brant, Kelly A; Fabisiak, James P.
Afiliación
  • Brant KA; University of Pittsburgh Graduate School of Public Health, Department of Environmental and Occupational Health, Bridgeside Point, 100 Technology Drive, Room 327, BRIDG, Pittsburgh, PA 15219-3130, USA. kab124@pitt.edu
Am J Respir Cell Mol Biol ; 38(5): 591-9, 2008 May.
Article en En | MEDLINE | ID: mdl-18096868
Particulate matter air pollution (PM) has been linked with chronic respiratory diseases. Real-life exposures are likely to involve a mixture of chemical and microbial stimuli, yet little attention has been paid to the potential interactions between PM components (e.g., Ni) and microbial agents on the development of inflammatory-like conditions in the lung. Using the Toll-like receptor (TLR)-2 agonist MALP-2 as a lipopeptide relevant to microbial colonization, we hypothesized that nickel sensitizes human lung fibroblasts (HLF) for microbial-driven chemokine release through modulation of TLR signaling pathways. NiSO(4) (200 muM) synergistically enhanced CXCL8, yet antagonized CXCL10 mRNA expression and protein release from HLF in response to MALP-2. RT(2)-PCR pathway-focused array results indicated that NiSO(4) exposure did not alter the expression of TLRs or their downstream signaling mediators, yet significantly increased the expression of cyclooxygenase 2 (COX-2). Moreover, when NiSO(4) was given in combination with MALP-2, there was an amplified induction of COX-2 mRNA and protein along with its metabolic product, PGE2, in HLF. The COX-2 inhibitor, NS-398, attenuated NiSO(4) and MALP-2-induced PGE2 and CXCL8 release and partially reversed the NiSO(4)-dependent inhibition of MALP-2-induced CXCL10 release from HLF. These data indicate that NiSO(4) alters the pattern of TLR-2-dependent chemokine release from HLF via a COX-2-mediated pathway. The quantitative and qualitative effects of NiSO(4) on microbial-driven chemokine release from HLF shed new light on how PM-derived metals can exacerbate respiratory diseases.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quimiocinas / Ciclooxigenasa 2 / Receptor Toll-Like 2 / Fibroblastos / Pulmón / Níquel Tipo de estudio: Qualitative_research Límite: Humans Idioma: En Revista: Am J Respir Cell Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2008 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quimiocinas / Ciclooxigenasa 2 / Receptor Toll-Like 2 / Fibroblastos / Pulmón / Níquel Tipo de estudio: Qualitative_research Límite: Humans Idioma: En Revista: Am J Respir Cell Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2008 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos