CARD14/CARMA2sh and TANK differentially regulate poly(I:C)–induced inflammatory reaction in keratinocytes

Abstract

CARD14/CARMA2sh (CARMA2sh) is a scaffold protein whose mutations are associated with the onset of human genetic psoriasis and other inflammatory skin disorders. Here we show that the immunomodulatory adapter protein TRAF family member-associated NF-κB activator (TANK) forms a complex with CARMA2sh and MALT1 in a human keratinocytic cell line. We also show that CARMA2 and TANK are individually required to activate the nuclear factor κB (NF-κB) response following exposure to polyinosinic-polycytidylic (poly [I:C]), an agonist of toll-like receptor 3. Finally, we present data indicating that TANK is essential for activation of the TBK1/IRF3 pathway following poly (I:C) stimulation, whereas CARMA2sh functions as a repressor of it. More important, we report that two CARMA2sh mutants associated with psoriasis bind less efficiently to TANK and are therefore less effective in suppressing the TBK1/IRF3 pathway. Overall, our data indicate that TANK and CARMA2sh regulate TLR3 signaling in human keratinocytes, which could play a role in the pathophysiology of psoriasis.

Enhanced Wound Healing- and Inflammasome-Associated Gene Expression in TNFAIP3-Interacting Protein 1- (TNIP1-) Deficient HaCaT Keratinocytes Parallels Reduced Reepithelialization

“…HaCaT keratinocytes, a spontaneously immortalized, nontumorigenic line [18], were cultured as previously described [13]. The HaCaT keratinocyte line has been extensively used to model human keratinocyte inflammatory pathway signaling, cytokine production, and reepithelialization [19][20][21][22][23][24][25][26]. TNIP1-targeting siRNA or nontargeting negative control siRNA was used to transfect HaCaT keratinocytes (triplicate wells plated as follows: 6well, 480,000 cells/well; 12-well, 160,000 cells/well; 24-well, 80,000 cells/well) 24 hr postplating.…”

Litchi Products as Dermatological Agents and Their Active Components

“…As described in the literature, poly(I:C) stimulated the expression of inflammatory factors, which were measured by the expression levels of IL-1β, IL-6, IL-8, TNF-α, and MCP-1 mRNA in cells. 30,31 Expression levels of IL-1β, IL-6, TNF-α, and MCP-1 were significantly higher following stimulation with poly(I:C) (p < 0.05). Although IL-8 levels were increased, this did not reach significance.…”

Potential skin health promoting benefits of costunolide: a therapeutic strategy to improve skin inflammation in imiquimod-induced psoriasis

“…Poly (I:C), a synthetic double-stranded ribonucleic acid (dsRNA) analog, is a potent TLR3 activator of IL-36γ expression and extracellular release, and is also widely used in psoriasis related studies. 21,[27][28][29] HMGB1 and IL-1β also play an important role in the inflammatory response. 23,30 Therefore, we established in vitro experiments stimulated with Poly(I:C).…”