Expression of the chloride channel CLCC1 is downregulated after 24 hours in LPS-primed THP-1 monocyte-like cell line

Abstract: Inflammation is the body's response to infection or injury and is mediated by the innate immune system. The NLRP3 inflammasome is a multi-protein complex that is a major contributor to many inflammatory disorders. Emerging evidence suggests the involvement of the Endoplasmic reticulum stress with the NLRP3 inflammasome. The endoplasmic reticulum stress is a series of stress signals that can activate the unfolded protein response and usually accompanies inflammation and eventually causes cell death. Recently, a localized endoplasmic reticulum micro-protein called the chloride clic like-1 channel was found to be involved in the endoplasmic reticulum homeostasis. Recent evidence suggests the involvement of endoplasmic reticulum stress in the inflammation pathways of the NLRP3 inflammasome. The relationship between the ER and the NLRP3 inflammasome has not been clearly described. This study aimed at investigating the expression levels of the microprotein CLCC1 to shed a light on the relationship between the endoplasmic reticulum stress and the NLRP3 inflammasome. The expression levels of CLCC1 were analyzed by qPCR in cultured monocytes under different time points of Lipopolysachaaride immuno-stimulation. The stability of expression in candidate reference genes was investigated for normalization purposes. This study reported the regulation of CLCC1 as a novel finding under prolonged LPS exposure of monocytes and stable reference genes such as GUSB and ACTB were identified. The relationship between CLCC1 and NLRP3 inflammasome priming by LPS indicated that CLCC1 is regulated and may be involved in the inflammatory mechanisms of endoplasmic reticulum stress and NLRP3 inflammasome inflammatory diseases, contributing to a potential therapeutic target in the endoplasmic reticulum and inflammasome related diseases.