Low pH environmental stress inhibits LPS and LTA-stimulated proinflammatory cytokine production in rat alveolar macrophages.
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 Ca²âº concentrations while Ca²âº 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 Ca²âº in low pH stress-induced signaling is complex but appears to be distinct between LPS- and LTA-mediated responses.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Fisiológico
/
Ácidos Teicoicos
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Lipopolisacáridos
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Citocinas
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Macrófagos Alveolares
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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