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Differential regulation of lipopolysaccharide and Gram‐positive bacteria induced cytokine and chemokine production in macrophages by Gα i proteins
Author(s) -
Fan Hongkuan,
Williams David L.,
Zingarelli Basilia,
Breuel Kevin F.,
Teti Giuseppe,
Tempel George E.,
Spicher Karsten,
Boulay Guylain,
Birnbaumer Lutz,
Halushka Perry V.,
Cook James A.
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02619.x
Subject(s) - chemokine , cytokine , lipopolysaccharide , macrophage inflammatory protein , biology , tumor necrosis factor alpha , microbiology and biotechnology , macrophage , immunology , chemistry , interleukin , inflammation , biochemistry , in vitro
Summary Heterotrimeric G i proteins play a role in signalling activated by lipopolysaccharide (LPS), Staphylococcus aureus (SA) and group B streptococci (GBS), leading to production of inflammatory mediators. We hypothesized that genetic deletion of G i proteins would alter cytokine and chemokine production induced by LPS, SA and GBS stimulation. LPS‐induced, heat‐killed SA‐induced and heat‐killed GBS‐induced cytokine and chemokine production in peritoneal macrophages from wild‐type (WT), Gα i2 –/– or Gα i1/3 –/– mice were investigated. LPS induced production of tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), IL‐10 and interferon‐γ‐inducible protein‐10 (IP‐10); SA induced TNF‐α, and IL‐1β production; and GBS induced TNF‐α, IL‐6, IL‐1β, macrophage inflammatory protein‐1α (MIP‐1α) and keratinocyte chemoattract (KC) production were all decreased ( P < 0·05) in Gα i2 –/– or Gα i1/3 –/– mice compared with WT mice. In contrast to the role of G i proteins as a positive regulator of mediators, LPS‐induced production of MIP‐1α and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) were increased in macrophages from Gα i1/3 –/– mice, and SA‐induced MIP‐1α production was increased in both groups of Gα i protein‐depleted mice. LPS‐induced production of KC and IL‐1β, SA‐induced production of GM‐CSF, KC and IP‐10, and GBS‐induced production of IL‐10, GM‐CSF and IP‐10 were unchanged in macrophages from Gα i2 –/– or Gα i1/3 –/– mice compared with WT mice. These data suggest that G i2 and G i1/3 proteins are both involved and differentially regulate murine inflammatory cytokine and chemokine production in response to both LPS and Gram‐positive microbial stimuli.