ASK Family Kinases Are Required for Optimal NLRP3 Inflammasome Priming.

ASK Family Kinases Are Required for Optimal NLRP3 Inflammasome Priming. Am J Pathol. 2018 Jan 15;: Authors: Place DE, Samir P, Karki R, Briard B, Vogel P, Kanneganti TD Abstract Activation of the multimeric inflammasome complex leads to inflammatory responses to biotic and abiotic triggers. The inflammasome sensor, Nod-like receptor family Pyrin domain containing 3 (NLRP3), is activated by a range of stimuli and is tightly regulated to restrict excessive inflammation. Because NLRP3 responds broadly to cellular insults and regulates cell death similar to the stress-activated apoptosis signal-regulating kinases 1 and 2 (ASK1/2), we hypothesized that ASK1/2 may regulate NLRP3 activity. Though essential for mediating NLRP3 inflammasome activation, ASK1/2 were not required for NLRC4 or absent in melanoma 2 (AIM2) inflammasome activation. ASK1/2 was required for NLRP3 up-regulation following lipopolysaccharide treatment in primary bone marrow-derived macrophages and lung fibroblasts as well as during infection with Burkholderia thailandensis and influenza virus. Consistent with reduced NLRP3 expression in response to B. thailandensis, caspase-1 cleavage and cell death were reduced in infected bone marrow-derived macrophages and mice lacking ASK1/2 were resistant to Burkholderia intranasal infection. Single knockouts of either ASK1 or ASK2 revealed a partial role for both ASK1 and ASK2 in NLRP3 up-regulation in response to LPS or B. thailan...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research