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Low pH environmental stress inhibits LPS and LTA-stimulated proinflammatory cytokine production in rat alveolar macrophages.
Fernandez, Stanley F; Fung, Christopher; Helinski, Jadwiga D; Alluri, Ravi; Davidson, Bruce A; Knight, Paul R.
Afiliación
  • Fernandez SF; Department of Medicine, Division of Cardiovascular Medicine, University at Buffalo, Suite 7030, 875 Ellicott Street, Buffalo, NY 14203, USA.
Biomed Res Int ; 2013: 742184, 2013.
Article en En | MEDLINE | ID: mdl-24288685
Gastric aspiration increases the risks for developing secondary bacterial pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs) is an important mechanism in initiating innate immune host response. Effects of low pH stress, a critical component of aspiration pathogenesis, on the PRR pathways were examined, specifically toll-like receptor-2 (TLR2) and TLR4, using isolated rat alveolar macrophages (aMØs). We assessed the ability of aMØs after brief exposure to acidified saline to elaborate proinflammatory cytokines in response to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation, known ligands of TLR4 and TLR2, respectively. Low pH stress reduced LPS- and LTA-mediated cytokine release (CINC-1, MIP-2, TNF-α, MCP-1, and IFN-ß). LPS and LTA increased intracellular Ca²âº concentrations while Ca²âº chelation by BAPTA decreased LPS- and LTA-mediated cytokine responses. BAPTA blocked the effects of low pH stress on most of LPS-stimulated cytokines but not of LTA-stimulated responses. In vivo mouse model demonstrates suppressed E. coli and S. pneumoniae clearance following acid aspiration. In conclusion, low pH stress inhibits antibacterial cytokine response of aMØs due to impaired TLR2 (MyD88 pathway) and TLR4 signaling (MyD88 and TRIF pathways). The role of Ca²âº in low pH stress-induced signaling is complex but appears to be distinct between LPS- and LTA-mediated responses.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Ácidos Teicoicos / Lipopolisacáridos / Citocinas / Macrófagos Alveolares / Exposición a Riesgos Ambientales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomed Res Int Año: 2013 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: Estrés Fisiológico / Ácidos Teicoicos / Lipopolisacáridos / Citocinas / Macrófagos Alveolares / Exposición a Riesgos Ambientales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomed Res Int Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos