Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • In the light of the above mentioned

    2022-01-24

    In the light of the above-mentioned considerations, it is interesting to note that the FPR-related research with regards to bias agonism did not prosper during considerably during the last decade (possible exceptions are [[8], [9], [10], [11]]. However, with new insights in receptor chemistry and further details to understand and exploit biased agonism in drug development we reckon it is now time to revisit FPRs to fight inflammatory and age-related diseases.
    Funding This work was supported by the German Research Foundation [DFG SFB1009/A06, SFB1348/A11]. Authors are members of the PHI Club of the Münster Alliance for Infection Research.
    Authorship
    Transparency document
    Introduction The immune system can recognize microbial molecular patterns in the form of peptides beginning with an N-formylated methionine, which is the first amino Shikonin inserted in new synthesized proteins/peptides in host cell mitochondria and prokaryotes [1,2]. Formyl peptide receptors (FPRs) are expressed by myeloid cells including granulocytes. Human neutrophils have two FPRs (FPR1 and FPR2) which feature a large sequence homology and produce overlapping functions [3,4]. These receptors belong to the 7-transmembrane G protein-coupled receptor family (GPCR) that controls a variety of host defense reactions [5,6]. It has been demonstrated that mouse neutrophils express orthologous of human FPR1 and FPR2, but the pharmacological differences between human and mouse receptors have not been fully characterized as yet [6,7]. The two receptors bind several peptides, which are pro-inflammatory mediators with chemotactic activity [8,9], and are also able to release reactive oxygen species (ROS) and granule constituents from immune cells. There are dual agonist that can bind both receptor, frequently with a preference for one or for the other [6]. FPR1 is the high affinity receptor for N-formyl-methionyl-phenylalanine (fMLF), while FPR2 is a low affinity receptor for fMLF. Indeed, agonists for FPR2 were initially identified as non-formylated peptides [[10], [11], [12]]. Considering the abundant presence of bacteria in the colon, it is plausible that formyl peptides may play a central role in the recruitment of neutrophils into inflammatory bowel diseases [13]. In vitro studies of cultured human colonic species [14] indicated that growth media of bacterial samples, isolated from the human gut, contain peptide fragments at concentrations comparable to 1 μM fMLF [15]. Moreover immunolocalization studies have identify Fpr1beside the membrane of crypt epithelial cells in normal colonic epithelium [16]. Commensal bacteria can release formylated peptides however how this phenomenon could impact on intestinal inflammation is not fully investigated. For instance, application of fMLF to the rodent intestinal lumen can increase microvascular permeability without promoting neutrophil infiltration [17,18] or, in a separate study, can increase recovery of neutrophil in the perfused segment [19]. Several studies have shown that fMLF is a powerful chemotactic factor for neutrophils and has been utilyzed experimentally to induce acute colitis in animal models [17,20], moreover patients with inflammatory bowel disease displayed FPR1+ve neutrophils [21]. Farooq and Stadnyk report that in DSS-induced colitis in Fpr1 gene-deficient mice produced little changes on the neutrophil infiltration in the acute phase of the pathology, while there was a higher degree of cell recruitment in the chronically inflamed colon [22]. Here we report that gene deletion of mouse Fpr1 markedly impacts on the macropscopic and microscopic features of DNBS colitis, leading to an outcome associated with marked upregulation of pro-inflammatory signalling in the inflamed colon.
    Materials and methods
    Results
    Discussion
    Authorships
    Conflict of interest
    Declaration of interest
    Funding
    Introduction The vascular wall and its compounds, including endothelial cells, are not static [[1], [2], [3]]. It was once accepted that the vascular smooth muscle cells (VSMCs) cytoskeleton remains stationary during a contractile event [1]. Now, it is recognized that the cytoskeleton displays a highly dynamic process characterized by polymerization and depolymerization of the cytoskeleton based upon cellular demand [3]. For example, pressure-induced actin polymerization in VSMCs is a mechanism underlying myogenic contraction [1].