Dataset Information


Role of IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) in mast cell response to lipopolysaccharide (LPS)

ABSTRACT: Mast cells are indispensable for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate sepsis. Tec family non-receptor tyrosine kinases ITK and BTK regulate mast cell-derived TNF-α in response to allergic antigen, but their role in LPS-induced TNF-α production by mast cells and related pathology is unclear. We sought to investigate the role(s) of ITK and BTK in mast cell response in septic condition. We found that the absence of ITK and BTK leads to enhanced TNF-α production by bone marrow-derived mast cells (BMMC). Itk-/-Btk-/- mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, along with enhanced expression of other related genes such as NF-κB targeted genes, compared to WT cells. Bone marrow cells from 8-week old WT, Itk-/-, Btk-/- and Itk-/-Btk-/- (double knockout: DKO) C57Bl/6 mice were cultured in murine Interleukin-3/Stem cell factor (IL-3/SCF) supplemented medium for 5 weeks to derive mast cells. WT, Itk-/-, Btk-/- and DKO bone marrow-derived mast cells (BMMC) were factor starved in medium without IL-3/SCF for 12 hours, followed by treatment with PBS (control) or 100 ng/ml LPS for 1 hour. Triplicates of each group were subjected to mouse whole genome genechip microarray analysis. Replicates were randomized on different chips to avoid systematic error.

ORGANISM(S): Mus musculus  

SUBMITTER: Avery August   Weishan Huang 

PROVIDER: E-GEOD-64287 | ArrayExpress | 2015-11-23



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Nonreceptor tyrosine kinases ITK and BTK negatively regulate mast cell proinflammatory responses to lipopolysaccharide.

Huang Weishan W   Morales J Luis JL   Gazivoda Victor P VP   August Avery A  

The Journal of allergy and clinical immunology 20151112 4

Mast cells are indispensable for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate septic responses. ITK and BTK regulate mast cell responses to allergens, but their roles in mast cell responses in LPS-induced sepsis are unclear.We sought to investigate the roles of ITK and BTK in mast cell responses during LPS-induced septic inflammation.Mice (genetically modified or bone marrow-derived mast cell-reconstituted Sash) were given LPS to induce septic hypothermia in  ...[more]

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