China
Africa
Explore chapters and articles related to this topic
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
S100A8 is also called calgranulin A or MRP8. S100A9 is also called calgranulin B or MRP14. At the time of discovery in 1987, they were actually called macrophage migration inhibitory factor (MIF)–related proteins: MRP8 and MRP14 (see Section 5.2.5.20). They preferentially form the S100A8/A9 heterodimer, which is called leukocyte protein L1 or cystic fibrosis antigen or calprotectin. These are abundantly expressed in myeloid cells, for example, neutrophils, monocytes, and early macrophages, and also to some extent in keratinocytes. In inflamed microvasculature, the S100A8/A9 complex is deposited onto the endothelium of venules associated with extravasating leukocytes. Normal tissue macrophages do not express S100A8/A9. Chronic inflammatory macrophages, for example, in RA, sarcoidosis, tuberculosis, or onchocerciasis, express both S100A8 and A9, but macrophages in acute inflammation usually express only S100A9. In neutrophils, the S100A8/A9 complex is the most abundant cytosolic protein and may represent almost 45% (30%–60%) of the soluble cytosolic protein content, and the level is 40-fold less in monocytes. This protein is also present in neutrophil granules, especially secondary granules, but the localization is blurred by the cytosolic abundance. IL10 indirectly and slowly stimulates S100A8/A9 production in a COX2-cAMP-dependent way, whereas Th2 cytokines IL4 and IL13 suppress them. Neutrophilic calprotectin, possibly largely cytosolic, is actively extruded with NETs, and this calprotectin is absolutely necessary for antifungal activity of NET in vitro.
Tazarotene
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Mark G. Lebwohl, Mild to Moderate Psoriasis, 2014
Monica Huynh, Chai Sue Lee, John Y. M. Koo
Tazarotenic acid, the active metabolite of tazarotene, binds to all three RAR subtypes, without having any effect on RXRs [5]. Retinoids elicit their biological effects by activating nuclear receptors and regulating gene transcription [6]. The exact molecular mechanism by which tazarotene is able to exert its effects on psoriasis is unknown, but it is thought to affect the three major pathogenic causes of psoriasis: in keratinocytes, tazarotene has antiproliferative effects, normalizes their abnormal differentiation, and decreases the expression of inflammatory markers on their cell surface [6]. Studies have shown that 0.05% tazarotene gel applied twice daily for 14 days improves keratinocyte differentiation through a reduction of hyperkeratosis and acanthosis and by reappearance of the granular layer [7]. Histochemically, pathogenic overexpression of epidermal differentiation markers such as involucrin, keratinocyte transglutaminase, skin-derived antileukoproteinase (also known as elafin), and migration inhibitory–related factor 8 (also known as calgranulin A) are significantly reduced [6]. In addition, tazarotene elevates markers such as filaggrin in psoriatic lesions, implicating a return to a more normal and quiescent skin status [7,8].
Seronegative arthropathies
Published in Rajan Madhok, Hilary Capell, The Year in Rheumatic Disorders Volume 4, 2004
BACKGROUND. Neutrophil, macrophage and lymphocytic infiltration are characteristic of the inflamed synovium in psoriatic and seronegative disease. Factors that regulate this inflammatory response have been much more poorly characterized than in RA. S100A12 (calgranulin C; or EN-RAGE), a member of a family of proteins that share EF hand domains, is produced predominantly by granulocytes and once secreted acts as a
Discerning the promising binding sites of S100/calgranulins and their therapeutic potential in atherosclerosis
Published in Expert Opinion on Therapeutic Patents, 2021
Harbinder Singh, Vikrant Rai, Devendra K Agrawal
The S100 proteins were first reported in 1965 with the characteristic feature of their solubility in 100% saturated ammonium sulfate solution at neutral pH, thus named as ‘S100 protein’ [24]. These proteins consist of 21 members which are mainly expressed in vertebrates and perform various intracellular and extracellular functions [25]. Among all the S100 proteins, S100A8, S100A9, and S100A12 are highly associated with cardiovascular disorders [18,26–28]. These three members of the S100 protein family are commonly referred to as S100/calgranulins. S100A8 is also known as calgranulin A and myeloid-related protein 8 (MRP-8). Similarly, S100A9 is also called calgranulin B and MRP-14. Their non-covalently combined form is also known as calprotectin (MRP8/14) which is a 24 kDa heterodimer of S100A8 and S100A9 (S100A8/A9) [29,30]. Likewise, calgranulin C or EN-RAGE are the other names of S100A12.
MiR-30a Regulates S100A12-induced Retinal Microglial Activation and Inflammation by Targeting NLRP3
Published in Current Eye Research, 2019
S100/calgranulin family comprises the largest group of calcium-binding proteins.7 All of the S100 proteins are characterized by the presence of two calcium-binding EF-hand motifs with different affinities for calcium.7 In the S100/calgranulin family, S100A8, S100A9, and S100A12 have been proved to play a pivotal role in exacerbating inflammatory response cooperating with inflammatory factors. S100A12 has been demonstrated to act independently from S100A8/S100A9, which is additionally known as EN-RAGE (extracellular newly identified receptor for AGE-binding protein).7,8 S100A12 is released from activated neutrophils and macrophages, which has proinflammatory effects on immune cells, and promotes inflammatory response.7–9 Our previous study has shown that plasma levels of S100A12 are closely associated with presence and severity of DR.9 However, to the best of our knowledge, whether S100A12 can contribute to the inflammatory changes of DR and microglial activation have not been fully elucidated.
Biomarkers for adult-onset still’s disease: up-to-date
Published in Expert Review of Molecular Diagnostics, 2019
Another candidate serologic marker in AOSD is the S100 proteins, the largest subgroup of calcium binding proteins. S100A8 (calgranulin A), A9 (calgranulin B), and A12 (calgranulin C) have been directly evaluated in AOSD [14–16]. S100 proteins are released by activated phagocytes, particularly granulocytes, as well as monocytes and macrophages, and represent one of the major inflammatory mediators of the innate immune response through toll-like receptor-4 activation. S100 proteins confer numerous regulatory functions in neutrophils, mononuclear cells, and mast cells, as well as a variety of extracellular functions including cell proliferation, and production of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α) and IL-1β. S100 proteins may also lead to activation of microvascular endothelial cells, resulting in increased junction permeability and up-regulation of thrombogenic factors [14]. Previous research has revealed that these markers are elevated in AOSD patients compared to RA and healthy controls (HC), and that they are correlated with several disease activity markers including the Pouchot score [15,16]. However, these studies did not compare S100 proteins with other febrile disorders, such as sepsis, lymphoproliferative diseases, and vasculitis, and they were single-centre studies with relatively small sample sizes.