Editorial: Exploring sulfur compounds’ role in inflammation and therapeutic potential

in treating COVID-19 and influenza by inactivating viral proteases and dampening the "cytokine storm".The final review paper in this special issue, by Hirabayashi et al., is dedicated to the enzymes that regulate intracellular RSS levels. The authors focus not only on the enzymes involved in the production of H2S and supersulfides including cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3MST), and CARS-but also on those responsible for their catabolism, namely sulfide:quinone oxidoreductase (SQOR), persulfide dioxygenase (ETHE1), and thiosulfate sulfurtransferase (TST). The manuscript provides a comprehensive overview of their roles in maintaining RSS homeostasis and their enzymatic reaction mechanisms. While this review is not exclusively focused on inflammatory processes, it provides valuable information regarding selective inhibitors targeting each of the individual enzymes involved in RSS regulation. As the authors emphasize, these inhibitors could serve as powerful tools for elucidating the biological functions of RSS in inflammation and may hold significant therapeutic potential.The original paper by Golenkina et al. explores how disulfide stress is linked to leukotriene synthesis. It is well-established that neutrophils are the primary immune cells recruited to the site of invading pathogens. When neutrophils interact with bacteria, they produce leukotriene B4 (LTB4), a powerful chemoattractant that, along with the principal bacterial chemoattractant i.e. N-formylmethionine-leucine-phenylalanine (fMLP), promotes the formation of neutrophil clusters around pathogens. Golenkina et al. investigated the regulating role of H2S in neutrophil cellular responses using an experimental model of neutrophils interacting with Salmonella typhimurium. Their findings demonstrate that under conditions of disulfide stress, which occurs during neutrophil-bacteria interactions, the use of the H2S donor supports the synthesis of LTB4, with a subsequent increase in the accumulation of neutrophils in bacterial clusters. This discovery can be used to search for innovative therapeutic interventions in bacterial infection states using H2S donors.The next interesting finding in this collection is related to the role of SO2 in mast cell activation-related diseases. It is known that mast cell degranulation is a critical step in allergic and inflammatory responses. Endogenous SO2 is an essential regulator of mitochondrial activity and is involved in the inflammatory response; however, the mechanism underpinning its participation in mast cell degranulation remained unknown until recently. The study by Song et al. elucidated that SO2 inhibits mast cell degranulation via the sulfenylation of galectin-9 (Gal-9) at cysteine 74 under both physiological and IgE-and non-IgE-stimulated pathophysiological conditions. This study identifies Gal-9 as an important regulatory molecule for controlling immune cell activity, and a biological target for therapeutic interventions. The development of drugs that stimulate sulfenylation of Gal-9 might provide a novel treatment approach for mast cell activation-related diseases.In conclusion, we believe that this special issue provides a profound exploration of the role of sulfur compounds in inflammation and offers a critical discussion of their therapeutic potential. In the published papers, the authors have presented the most up-to-date information on the roles of reactive sulfur species (RSS)-primarily H2S, persulfides, polysulfides, and SO2-in inflammatory diseases. It should be emphasized that the biological effects of RSS are bidirectional and context-dependent. Specifically, they can either promote or suppress immune responses, depending on their concentration and the cellular redox environment. These factors must be carefully considered in future research and in the establishment of dose-response relationships for clinical applications.