Methylarginine Levels in Chronic Inflammatory Skin Diseases-The Role of L-Arginine/Nitric Oxide Pathway

In recent years, the L-arginine/nitric oxide (NO) pathway has garnered increasing attention across a range of pathological conditions, including skin diseases. NO is an important modulator of skin homeostasis, being actively involved in numerous processes such as vasodilation, keratinocyte proliferation, melanogenesis and cell signaling. Under inflammatory conditions, post-translational changes in L-arginine take place, resulting in the synthesis of methylarginines including monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). Once ADMA and MMA are generated, they compete with L-arginine to bind to the active site of NO synthase, which reduces the production of NO. Additionally, SDMA inhibits the transport of L-arginine, leading to a lower concentration of this amino acid within cells. Consequently, by impacting both the availability of L-arginine and the production of NO, conditions favoring oxidative stress and endothelial dysfunction are created. Dysregulation of L-arginine/NO pathway is closely related to inflammation and oxidative stress, two events that play a cardinal role in the pathogenesis of chronic inflammatory skin diseases. We conducted a narrative review that synthesizes current evidence on methylarginine levels in patients with chronic inflammatory skin diseases. Our aim was to enhance our knowledge about the role of these compounds in pathogenesis and provide new insights into the mechanisms underlying these conditions that can be the basis for novel diagnostic biomarkers and therapies.