Altered Expression of Dual-Specificity Phosphatases in Macrophages Exposed to Lipid Nanoparticles

Acute inflammation is rapidly elicited in response to pathogens, toxins, and other cellular components that interact with immune cells through surface receptors, activating signaling cascades that lead to the expression of molecules aimed at neutralizing the pathogen and stimulating other cells to begin the healing process. However, a robust inflammatory response can be detrimental if it is prolonged. Therefore, the inflammatory response must be tightly regulated to prevent secondary harmful effects. In this regard, cells contain molecular switches that turn the inflammatory process on and off. The rapid response to infection and injury is mediated by constitutive cellular proteins that are activated by posttranslational modifications, of which phosphorylation is the most common. Consequently, compensatory mechanisms often involve the removal of phosphate groups by phosphatases. A family of phosphatases known as dual-specificity phosphatases (DUSPs), which dephosphorylate both tyrosine and serine/threonine residues, has emerged as a critical mechanism for controlling inflammation. To date, more than 40 DUSPs have been identified in the human genome. Despite their shared catalytic specificity, they appear to participate in diverse cellular processes and are expressed in response to various stimuli. In the present study, we detected a distinctive pattern of DUSP expression in response to exogenous lipid nanoparticles and toxins. These observations suggest that the transcriptional regulation of several DUSPs may be coordinated. They also raise the possibility that DUSPs may play redundant roles to ensure the proper resolution of the inflammatory response.