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      Role of chemokines in regulating luteal and uterine functions in pregnant cows

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          Abstract

          Pregnancy is intricately regulated by the interactions between various bioactive substances secreted by the conceptus, uterus, and corpus luteum (CL). Interferon-τ, synthesized and secreted by the conceptus, plays a central role in the interaction mechanism of maternal recognition in cows. Chemokines, chemotaxis mediators that are primarily secreted by immune cells, regulate various reproductive responses in various species. Although there are scattered reports on the potential roles of chemokines in the bovine CL and the uterus during the estrous cycle, there is little information on chemokines in these organs during pregnancy. Therefore, in this review, we discuss the possible physiological roles of chemokines in the CL and uterus of pregnant cows, focusing on our recent findings on chemokines and changes in their receptor expression in the CL and endometrium of cows at some stages of pregnancy.

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          Most cited references76

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          Lymphocyte traffic control by chemokines.

          In contrast to the remarkable chemokine responses of phagocytes and monocytes that were documented early on, lymphocytes have been considered for a long time to be poor targets for chemokine action. This view has changed dramatically with the discovery that peripheral blood T cells need to be activated before they can migrate in response to inflammatory chemokines. These chemokines do not act on the bulk of resting T cells that are in circulation. The identification of a new group of chemokines that selects resting, as opposed to effector, T and B cells was very exciting. These inflammation-unrelated chemokines affect transendothelial migration and localization of progenitor and mature lymphocytes in lymphoid and nonlymphoid tissues. Here, we summarize the current view of chemokine-mediated lymphocyte traffic and focus on the molecular mechanisms by which T cell responses to chemokines are modulated. Recent developments in this area justify the hypothesis that the distinct migration patterns of lymphocytes throughout their life cycle--that is, during lymphopoiesis, antigen-dependent priming, inflammation and immune surveillance--are finely tuned by changing sets of chemokines that are selective for developmentally regulated chemokine receptors. Thus, the chemokine system assures that cell traffic during inflammatory responses occurs in the proper spatial and temporal fashion and disturbance of this system, therefore, can lead to inflammatory disease.
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            An Alternatively Spliced Variant of CXCR3 Mediates the Inhibition of Endothelial Cell Growth Induced by IP-10, Mig, and I-TAC, and Acts as Functional Receptor for Platelet Factor 4

            The chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte proliferation, and act as angiostatic agents, thus inhibiting tumor growth. These multiple activities are apparently mediated by a unique G protein–coupled receptor, termed CXCR3. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including a powerful angiostatic effect, but its specific receptor is still unknown. Here, we describe a distinct, previously unrecognized receptor named CXCR3-B, derived from an alternative splicing of the CXCR3 gene that mediates the angiostatic activity of CXCR3 ligands and also acts as functional receptor for CXCL4. Human microvascular endothelial cell line-1 (HMEC-1), transfected with either the known CXCR3 (renamed CXCR3-A) or CXCR3-B, bound CXCL9, CXCL10, and CXCL11, whereas CXCL4 showed high affinity only for CXCR3-B. Overexpression of CXCR3-A induced an increase of survival, whereas overexpression of CXCR3-B dramatically reduced DNA synthesis and up-regulated apoptotic HMEC-1 death through activation of distinct signal transduction pathways. Remarkably, primary cultures of human microvascular endothelial cells, whose growth is inhibited by CXCL9, CXCL10, CXCL11, and CXCL4, expressed CXCR3-B, but not CXCR3-A. Finally, monoclonal antibodies raised to selectively recognize CXCR3-B reacted with endothelial cells from neoplastic tissues, providing evidence that CXCR3-B is also expressed in vivo and may account for the angiostatic effects of CXC chemokines.
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              CXC chemokines in angiogenesis.

              CXC chemokines display pleiotropic effects in immunity, regulating angiogenesis, and mediating organ-specific metastases of cancer. In the context of angiogenesis, CXC chemokines are a unique family of cytokines, known for their ability to behave in a disparate manner in the regulation of angiogenesis. Members that contain the 'ELR' motif are potent promoters of angiogenesis, and mediate their angiogenic activity via binding and activating CXCR2 on endothelium. In contrast, members, in general, those are inducible by interferons and lack the ELR motif (ELR-) are potent inhibitors of angiogenesis, and bind to CXCR3 on endothelium. This review will discuss the biology of these angiogenic and angiostatic CXC chemokines and discuss their disparate angiogenic activity in the context of a variety of disorders.
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                Author and article information

                Journal
                J Reprod Dev
                J Reprod Dev
                JRD
                The Journal of Reproduction and Development
                The Society for Reproduction and Development
                0916-8818
                1348-4400
                25 February 2024
                June 2024
                : 70
                : 3
                : 145-151
                Affiliations
                [1) ]Division of Advanced Feeding Technology Research, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization (NARO), Ibaraki 305-0901, Japan
                [2) ]Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8577, Japan
                Author notes
                Correspondence: R Sakumoto (e-mail: sakumoto@ 123456affrc.go.jp )
                Article
                2023-100
                10.1262/jrd.2023-100
                11153120
                38403584
                b71ad931-e76f-4a5a-be7f-bd904afa5b6e
                ©2024 Society for Reproduction and Development

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)

                History
                : 13 December 2023
                : 02 February 2024
                Categories
                SRD Outstanding Research Award 2023

                chemokines,corpus luteum,cow,pregnancy,uterus
                chemokines, corpus luteum, cow, pregnancy, uterus

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