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      The role of inflammation in silicosis

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          Abstract

          Silicosis is a chronic illness marked by diffuse fibrosis in lung tissue resulting from continuous exposure to SiO 2-rich dust in the workplace. The onset and progression of silicosis is a complicated and poorly understood pathological process involving numerous cells and molecules. However, silicosis poses a severe threat to public health in developing countries, where it is the most prevalent occupational disease. There is convincing evidence supporting that innate and adaptive immune cells, as well as their cytokines, play a significant role in the development of silicosis. In this review, we describe the roles of immune cells and cytokines in silicosis, and summarize current knowledge on several important inflammatory signaling pathways associated with the disease, aiming to provide novel targets and strategies for the treatment of silicosis-related inflammation.

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          Most cited references156

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          The nuclear factor NF-kappaB pathway in inflammation.

          The nuclear factor NF-kappaB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-kappaB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic evidence in mice has revealed complex roles for the NF-kappaB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway. NF-kappaB has long been considered the "holy grail" as a target for new anti-inflammatory drugs; however, these recent studies suggest this pathway may prove a difficult target in the treatment of chronic disease. In this article, we discuss the role of NF-kappaB in inflammation in light of these recent studies.
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            Mechanism and Regulation of NLRP3 Inflammasome Activation.

            Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed 'inflammasomes'. The biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL-1β) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanism and regulation of its activation remain unclear. In this review we summarize current understanding of the mechanism and regulation of NLRP3 inflammasome activation as well as recent advances in the noncanonical and alternative inflammasome pathways.
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              Monocyte chemoattractant protein-1 (MCP-1): an overview.

              Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.
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                Author and article information

                Contributors
                Role:
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                URI : https://loop.frontiersin.org/people/878883/overviewRole:
                URI : https://loop.frontiersin.org/people/2584425/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/1075883/overviewRole:
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                07 March 2024
                2024
                : 15
                : 1362509
                Affiliations
                Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, China
                Author notes

                Edited by: Giulio Cabrini, University of Ferrara, Italy

                Reviewed by: Jennifer Speth, University of Michigan, United States

                Steven Eugene Mutsaers, University of Western Australia, Australia

                *Correspondence: Yun Zhan, zhanyun@ 123456imm.ac.cn
                Article
                1362509
                10.3389/fphar.2024.1362509
                10955140
                38515835
                b4eb3521-77ac-4972-b5c7-d1b8103f7f8b
                Copyright © 2024 Liu, Sun, Han, Zhan and Jiang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 December 2023
                : 21 February 2024
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the CAMS Innovation Fund for Medical Sciences (2022-I2M-2-002, 2022-12M-1-016).
                Categories
                Pharmacology
                Review
                Custom metadata
                Respiratory Pharmacology

                Pharmacology & Pharmaceutical medicine
                silicosis,inflammation,immune cells,cytokines,signal pathway

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