THE HUMAN-RESTRICTED DUPLICATED FORM OF THE alpha7 NICOTINIC RECEPTOR, CHRFAM7A: EXPRESSION, TRANSCRIPTIONAL REGULATION AND ROLE IN THE INFLAMMATORY PROCESS

Inflammation is the host's physiological response to pathogen invasion and tissue damage. It is essential for survival, but at the same time, if not kept under control by endogenous mechanisms, can cause serious morbidity, both acute and chronic. One mechanism of controlling the host's inflammatory response relies on the activity of the "Cholinergic anti-inflammatory pathway", where the afferent component of the vagus nerve, by sensing the inflammatory processes that occur at the peripheral level, release acetylcholine (ACh) to reduce the level of pro-inflammatory cytokines. Various studies have shown that the ?7 nicotinic receptor (CHRNA7) is a key element for the functioning of this pathway. Recently, CHRFAM7A gene was discovered in humans. It is the product of a recombination event occurred on chromosome 15 (15q13-q14 region), 1.6 Mb apart from CHRNA7 gene, where the portion of CHRNA7 gene, from exon 5 to 10, fused in frame to a novel gene (FAM7A), giving raise to a nAChR subunit differing from CHRNA7 for its N-terminus. Our laboratory has shown that LPS treatment down-regulated the expression of the CHRFAM7A gene in THP-1 cell lines and primary cultures of macrophages, mainly by a transcriptional mechanism reliant on NF-?B. Conversely, LPS induced the expression of the CHRNA7 gene suggesting that in these cells CHRFAM7A may participate specifically in the innate immune system's inflammatory response by acting as a dominant negative regulator of the ?7 nicotinic receptor. The identification and characterization of CHRFAM7A gene's regulatory region which is, to date, unknown, will be presented.