Naja kaouthia venom protein, Nk-CRISP, upregulates inflammatory gene expression in human macrophages.

Naja kaouthia venom protein, Nk-CRISP, upregulates inflammatory gene expression in human macrophages. Int J Biol Macromol. 2020 May 26;: Authors: Deka A, Sharma M, Mukhopadhyay R, Devi A, Doley R Abstract Cysteine-Rich Secretory Proteins (CRISP) are widespread in snake venoms and known to target ion channels. More recently, CRISPs have been shown to mediate inflammatory responses. Involvement of potential receptor in CRISP-induced inflammatory reactions, however, remains unknown. A CRISP protein named as Nk-CRISP, was isolated from the venom of Naja kaouthia. The molecular mass of the purified protein was found to be ~25 kDa and the primary sequence was determined by MALDI TOF-TOF. The involvement of this protein in proinflammatory effects were evaluated in THP-1 macrophage-like cells. Nk-CRISP treated cells induced up-regulation of several inflammatory marker genes in dose dependent manner. Toll like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex are known to play crucial role in recognition of damage/pathogen-associated molecular patterns and activation of innate immune response. Therefore, we hypothesized that snake venom CRISP could also modulate the innate immune response via TLR4-MD2 complex. In-silico molecular docking study of cobra CRISP with TLR4-MD2 receptor complex reveals Nk-CRISP engages cysteine-rich domain (CRD) to interact with complex. Inhibition of TLR4 signalling pathway using CLI-095 confirmed...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research