Nitric oxide (NO) is a free radical molecule expressed in some dendritic cells (DCs) and related cells in the intestine and involved in intestinal immunoglobulin A (IgA) synthesis. It is synthesized from L-arginine by three different isoforms of NO synthase (NOS): neuronal NOS (encoded by Nos1), inducible NOS (iNOS, encoded by Nos2), and endothelial NOS (encoded by Nos3).NO has neurotransmitter, immunomodulator, and vasodilator properties. NO exerts its effects through two pathways: heme iron- and S-nitrosylation. In the heme iron pathway, NO activates soluble guanylate cyclase (sGC), which converts guanosine monophosphate (GMP) into cyclic GMP, a second messenger that activates protein kinase G. In the S-nitrosylation pathway, NO controls the activity of various intracellular signaling molecules, including enzymes and transcription factors, through S-nitrosylation of the cysteine thiol group.
In the context of homeostatic inflammation, the role of NO becomes very relevant. Inducible Nitric Oxide Synthase (iNOS), which is produced within dendritic cells and macrophages, plays a significant role in this context. When exposed to bacterial elements and inflammatory cytokines, iNOS facilitates the production of large amounts of NO. This production of NO is highly effective in killing bacteria. Looking closer at the gut-associated lymphoid tissue (GALT), there is continuous stimulation by harmless resident bacteria, which triggers iNOS expression and subsequently leads to NO production within the dendritic cells. This phenomenon, known as "homeostatic inflammation," is vital for the production of IgA.
