Showing papers on "Serum amyloid A1 published in 2018"
TL;DR: Proteolytic cleavage of SAA1 by MMP-9 fine tunes the inflammatory capacity of this acute phase protein in that only the synergistic interactions with chemokines remain to prolong the duration of inflammation.
Abstract: Serum amyloid A1 (SAA1) is a prototypic acute phase protein, induced to extremely high levels by physical insults, including inflammation and infection. Human SAA and its NH2-terminal part have been studied extensively in the context of amyloidosis. By contrast, little is known about COOH-terminal fragments of SAA. Intact SAA1 chemoattracts leukocytes via the G protein-coupled receptor formyl peptide receptor like 1/formyl peptide receptor 2 (FPR2). In addition to direct leukocyte activation, SAA1 induces chemokine production by signaling through toll-like receptor 2. We recently discovered that these induced chemokines synergize with intact SAA1 to chemoattract leukocytes in vitro and in vivo. Gelatinase B or matrix metalloproteinase-9 (MMP-9) is also induced by SAA1 during infection and inflammation and processes many substrates in the immune system. We demonstrate here that MMP-9 rapidly cleaves SAA1 at a known consensus sequence that is also present in gelatins. Processing of SAA1 by MMP-9 at an accessible loop between two alpha helices yielded predominantly three COOH-terminal fragments: SAA1(52-104), SAA1(57-104), and SAA1(58-104), with a relative molecular mass of 5,884.4, 5,327.3, and 5,256.3, respectively. To investigate the effect of proteolytic processing on the biological activity of SAA1, we chemically synthesized the COOH-terminal SAA fragments SAA1(52-104) and SAA1(58-104) and the complementary NH2-terminal peptide SAA1(1-51). In contrast to intact SAA1, the synthesized SAA1 peptides did not induce interleukin-8/CXCL8 in monocytes or fibroblasts. Moreover, these fragments possessed no direct chemotactic activity for neutrophils, as observed for intact SAA1. However, comparable to intact SAA1, SAA1(58-104) cooperated with CXCL8 in neutrophil activation and migration, whereas SAA1(1-51) lacked this potentiating activity. This cooperative interaction between the COOH-terminal SAA1 fragment and CXCL8 in neutrophil chemotaxis was mediated by FPR2. Hence, proteolytic cleavage of SAA1 by MMP-9 fine tunes the inflammatory capacity of this acute phase protein in that only the synergistic interactions with chemokines remain to prolong the duration of inflammation.
17 citations
TL;DR: A significant association between T allele of rs12218 and AOSD in Japanese population is shown and there was no significant difference in SAA1 -13C/T allele frequency between AOSd patients with and without MEFV mutations.
15 citations
TL;DR: It is demonstrated that the human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute phase protein, and the abundance of SAA1 in the amnion was increased at parturition.
Abstract: PROBLEM Rupture of fetal membranes is a crucial event at parturition, which is preceded by extensive extracellular matrix (ECM) remodeling. Our recent studies have demonstrated that the human fetal membranes are capable of de novo synthesis of serum amyloid A1 (SAA1), an acute phase protein, and the abundance of SAA1 in the amnion was increased at parturition. However, the exact role of SAA1 in human parturition remains to be established. METHOD OF STUDY The effects of SAA1 on the abundance of collagenases and lysyl oxidase, the enzyme that cross-links collagens, were investigated in culture primary human amnion fibroblasts and tissue explants with an aim to examine the involvement of SAA1 in the ECM remodeling in the amnion. RESULTS Serum amyloid A1 (SAA1) time- and dose-dependently increased the abundance of collagenases MMP-1, MMP-8, and MMP-13, while decreased the abundance of lysyl oxidase-like 1 (LOXL1). These effects of SAA1 were attenuated by siRNA-mediated knockdown of the Toll-like receptor (TLR) 4 and its antagonist CLI-095, but not by siRNA-mediated knockdown of TLR2. Furthermore, the inhibitors for NF-κB (JSH-23) and mitogen-activated protein kinases (MAPKs) p38 (SB203580) and JNK (SP600125) could also attenuate the effects of SAA1, while the inhibitor for MAPK ERK1/2 (PD 98059) could block the effects of SAA1 only on MMP-1, MMP-8, and LOXL1 but not on MMP-13. CONCLUSION These data highlight a possible role for SAA1 in ECM remodeling preceding membrane rupture by regulating the expression of collagenases MMP-1, MMP-8, MMP-13, and LOXL1 through TLR4-mediated activation of the NF-κB and MAPK pathways in amnion fibroblasts.
11 citations
TL;DR: It is shown that SAA1 induces intestinal epithelial cell migration, spreading, and attachment through a formyl peptide receptor 2-dependent mechanism and provides evidence for a physiological role in the wound environment.
Abstract: Several proteins endogenously produced during the process of intestinal wound healing have demonstrated prorestitutive properties. The presence of serum amyloid A1 (SAA1), an acute-phase reactant, within inflamed tissues, where it exerts chemotaxis of phagocytes, is well recognized; however, a putative role in intestinal wound repair has not been described. Herein, we show that SAA1 induces intestinal epithelial cell migration, spreading, and attachment through a formyl peptide receptor 2–dependent mechanism. Induction of the prorestitutive phenotype is concentration and time dependent and is associated with epithelial reactive oxygen species production and alterations in p130 Crk-associated substrate staining. In addition, using a murine model of wound recovery, we provide evidence that SAA1 is dynamically and temporally regulated, and that the elaboration of SAA1 within the wound microenvironment correlates with the influx of SAA1/CD11b coexpressing immune cells and increases in cytokines known to induce SAA expression. Overall, the present work demonstrates an important role for SAA in epithelial wound recovery and provides evidence for a physiological role in the wound environment.
11 citations
TL;DR: It is suggested that AuNPs may potentially induce SAA1-TLR2-mediated NF-kB transcription factor activation in lung epithelial cells, highlighting that nano-bio interactions could result in biological effects that may affect cells.
9 citations
TL;DR: This work has detected a ∼ 12‐kDa protein reacting with antibodies against serum amyloid A (SAA) in human colostrum by western blotting and identified the reactive species as SAA1, previously identified as a prominent member of the acute‐phase response in serum.
9 citations
2 citations
Patent•
01 Nov 2018
TL;DR: In this article, a human serum amyloid A1 functional oligopeptide (SAA1) was derived from the amino acid sequence of the human serum A1 and a polypeptide fragment was obtained from the Mth to the Nth amino acids of a full-length amino acid sequences (104 amino acids) of SAA1.
Abstract: Disclosed is a human serum amyloid A1 functional oligopeptide, and a preparation method therefor and an application thereof. Specifically, the present invention provides a human serum amyloid A1 polypeptide fragment, or a pharmacologically acceptable salt thereof. The polypeptide fragment comprises the following characteristics: (i) the sequence of the polypeptide fragment is derived from the amino acid sequence of the human serum amyloid A1; and (ii) the polypeptide fragment is derived from the Mth to the Nth amino acids of a full-length amino acid sequence (104 amino acids) of the human serum amyloid A1 (SAA1), and has a length of 42-67 amino acids, wherein M is any positive integer from 9 to 14, and N is any positive integer from 55 to 75. The human serum amyloid functional oligopeptide in the present invention has the capability of inhibiting expression of pro-inflammatory cytokines and promoting expression of anti-inflammatory cytokines, and can be used for preparing drugs treating inflammatory diseases.
Patent•
02 Nov 2018
TL;DR: The human serum amyloid functional short peptide (SAA1) as mentioned in this paper has the capabilities of inhibiting proinflammatory cytokine expression and promoting anti-inflammatory cell factor expression, and can be used for preparing medicines for treating inflammatory diseases.
Abstract: The invention discloses human serum amyloid A1 functional short peptide as well as a preparation method and application thereof. Particularly, the invention provides a human serum amyloid A1 polypeptide segment or pharmaceutically acceptable salt, wherein the polypeptide segment has the following characteristics that (i) a sequence of the polypeptide segment is derived from an amino acid sequenceof the human serum amyloid A1; (ii) the polypeptide segment comes from the Mth bit to the Nth bit of a whole-length amino acid sequence (104 amino acid) of the human serum amyloid A1 (SAA1), and the length is 42 to 67 amino acid, wherein M is any one positive integer from 9 to 14, and N is any one positive integer from 55 to 75. The human serum amyloid functional short peptide disclosed by the invention has the capabilities of inhibiting proinflammatory cytokine expression and promoting anti-inflammatory cell factor expression, and can be used for preparing medicines for treating inflammatorydiseases.