Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi in Psoriasis and Psoriatic Arthritis, 2017
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
John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Mark G. Lebwohl in Mild to Moderate Psoriasis, 2014
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].
The Scientific Basis of Urinary Stone Formation
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
One factor that may affect the kinetics of the processes involved in both theories is the presence or absence in urine of so-called modifiers of crystallization (8). These are claimed to be of particular importance in the formation of calcium-containing stones. Indeed, no specific, naturally occurring modifier has been reported to have any effect on the crystallization of cystine, uric acid or magnesium ammonium phosphate. One group of crystallization modifiers is claimed to retard the rate of growth and/or aggregation of crystals of calcium salts and/or the binding of calcium-containing crystals to cell walls. These are known as inhibitors of crystallization and include magnesium (33), citrate (34), pyro-phosphate (35,36), adenosine diphosphate (37), adenosine triphosphate (37), at least two phosphopeptides (38), various glycosaminoglycans (39,40), nonpolymerised Tamm-Horsfall protein (also known as uromodulin) (41,42), nephrocalcin (43–46), calgranulin (47), various plasma proteins (12), osteopontin (also known as uropontin) (48,49), a-1-microglobulin (13), β-2-microglobulin (50), urinary prothrombin fragment 1 (51,52) and inter-α-trypsin inhibitor (bikunin light chain) (53,54).
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.
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.
A shotgun proteomic approach reveals novel potential salivary protein biomarkers for asthma
Published in Journal of Asthma, 2022
Orapan Poachanukoon, Sittiruk Roytrakul, Sittichai Koontongkaew
S100A2 is a member of a family of the S100/calgranulin Ca++‐binding proteins implicated in a number of inflammatory diseases (28). Little is known about the role of S100A2 in human asthmatics compared to S100A8/A9 (29,30) and S100A12 (31,32). S100A2 gene was less upregulated in bronchial epithelial cells of asthmatic patients than normal subjects in response to ozone exposure and virus infection (33). Little is known about the function of ZNF263, except that it may have a repressive effect on gene transcription and often binds intragenic regions (34). ZNF263 is involved in the development of the many complex diseases associated with stress and aging (35).
Related Knowledge Centers
- Calcium Oxalate
- Epithelium
- Protein Dimer
- Neutrophil
- S100 Protein
- Kidney
- S100A8
- S100A9
- Calprotectin
- S100A12