1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Understanding the Complexity of Sjögren’s Syndrome: Remarkable Progress in Elucidating NF-κB Mechanisms

      review-article
      * , ,
      Journal of Clinical Medicine
      MDPI
      Sjögren’s syndrome, NF-κB, inflammation

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Sjögren’s syndrome (SS) is a systemic autoimmune inflammatory disease with a poorly defined aetiology, which targets exocrine glands (particularly salivary and lachrymal glands), affecting the secretory function. Patients suffering from SS exhibit persistent xerostomia and keratoconjunctivitis sicca. It is now widely acknowledged that a chronic grade of inflammation plays a central role in the initiation, progression, and development of SS. Consistent with its key role in organizing inflammatory responses, numerous recent studies have shown involvement of the transcription factor nuclear factor κ (kappa)-light-chain-enhancer of activated B cells (NF-κB) in the development of this disease. Therefore, chronic inflammation is considered as a critical factor in the disease aetiology, offering hope for the development of new drugs for treatment. The purpose of this review is to describe the current knowledge about the NF-κB-mediated molecular events implicated in the pathogenesis of SS.

          Related collections

          Most cited references117

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          NF-κB signaling in inflammation

          The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The NF-kappaB family of transcription factors and its regulation.

            Nuclear factor-kappaB (NF-kappaB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappaB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappaB proteins (IkappaBs), which retain inactive NF-kappaB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappaB activation converge on the IkappaB kinase (IKK) complex, which is responsible for IkappaB phosphorylation and is essential for signal transduction to NF-kappaB. Additional regulation of NF-kappaB activity is achieved through various post-translational modifications of the core components of the NF-kappaB signaling pathways. In addition to cytosolic modifications of IKK and IkappaB proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappaB response. This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Signaling to NF-kappaB by Toll-like receptors.

              Innate immunity is the first line of defense against invading pathogens. A family of Toll-like receptors (TLRs) acts as primary sensors that detect a wide variety of microbial components and elicit innate immune responses. All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-kappaB (NF-kappaB), which controls the expression of an array of inflammatory cytokine genes. NF-kappaB activation requires the phosphorylation and degradation of inhibitory kappaB (IkappaB) proteins, which is triggered by two kinases, IkappaB kinase alpha (IKKalpha) and IKKbeta. In addition, several TLRs activate alternative pathways involving the IKK-related kinases TBK1 [TRAF family member-associated NF-kappaB activator (TANK) binding kinase-1] and IKKi, which elicit antiviral innate immune responses. Here, we review recent progress in our understanding of the role of NF-kappaB in TLR signaling pathways and discuss potential implications for molecular medicine.
                Bookmark

                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                31 August 2020
                September 2020
                : 9
                : 9
                : 2821
                Affiliations
                Department of Basic Medical Sciences, Neurosciences and Sensory Organs (SMBNOS), Section of Human Anatomy and Histology, University of Bari “Aldo Moro”, 70124 Bari, Italy; domenico.ribatti@ 123456uniba.it (D.R.); sabrina.lisi@ 123456uniba.it (S.L.)
                Author notes
                [* ]Correspondence: margherita.sisto@ 123456uniba.it ; Tel.: +39-080-547-8315; Fax: +39-080-547-8327
                Author information
                https://orcid.org/0000-0001-8349-1121
                https://orcid.org/0000-0003-4768-8431
                Article
                jcm-09-02821
                10.3390/jcm9092821
                7563658
                32878252
                4bd310a9-6b1c-4002-8a29-1168f49f5719
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 July 2020
                : 28 August 2020
                Categories
                Review

                sjögren’s syndrome,nf-κb,inflammation
                sjögren’s syndrome, nf-κb, inflammation

                Comments

                Comment on this article