Toll-like receptor agonists, poly(I:C) and flagellin, lead to IL-36g induction with divergent release kinetics and differentially alter autophagy in primary human keratinocytes
Christopher J. Papayannakos1,*, Daniel Zhu1,*, Bongseok Jung2, Ali A. Rana2, James A. DeVoti2,3, Allan L. Abramson4, Vincent R. Bonagura2,3, Bettie M. Steinberg2,5
European Cytokine Network, Vol.33, No.2, pp. 19-29, 2022, DOI:10.1684/ecn.2022.0479
Abstract IL-36γ, a pro-inflammatory member of the IL-1 cytokine superfamily, can be induced and secreted by normal human foreskin keratinocytes (HFKs) in response to pathogenic stimuli, however, the mechanisms underlying the secretion are unknown. In this study, we demonstrate that stimulation with the TLR3 agonist, poly (I:C), led to a delayed secretion of IL-36γ compared to stimulation with the TLR5 agonist, flagellin, despite equal levels of the cytokine (p = 0.006). IL-36γ was shown to be released from HFKs in its inactive, uncleaved form, based on western blotting. Moreover, recombinant IL-36γ in its activated, cleaved form… More >
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