{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:38:31Z","timestamp":1760146711133,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council of Hong Kong","award":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"],"award-info":[{"award-number":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"]}]},{"name":"University Grants Committee of Hong Kong","award":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"],"award-info":[{"award-number":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"]}]},{"name":"National Key Basic Research Program of China","award":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"],"award-info":[{"award-number":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"]}]},{"name":"Innovation and Technology Commission of Hong Kong","award":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"],"award-info":[{"award-number":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"]}]},{"name":"Hong Kong Jockey Club","award":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"],"award-info":[{"award-number":["16102018","AoE\/M-604\/16","2013CB530900","ITCPD\/17-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Communications between different cell types within a tissue are often critical for the proper functioning of an organ. In the central nervous system, interactions among neurons and glial cells are known to modulate neurotransmission, energy metabolism, extracellular ion homeostasis, and neuroprotection. Here we showed that bradykinin, a proinflammatory neuropeptide, can be detected by astrocytes, resulting in the secretion of cytokines that act on neurons. In astrocytic cell lines and primary astrocytes, bradykinin and several other ligands acting on Gq-coupled receptors stimulated Ca2+ mobilization, which subsequently led to the release of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). The bradykinin B2 receptor antagonist, HOE-140, effectively blocked the ability of bradykinin to mobilize Ca2+ and stimulate mitogen-activated protein kinases (MAPKs) in astrocytes. Interestingly, incubation of neuronal cell lines and primary cortical neurons with conditioned media from bradykinin-treated astrocytes resulted in the activation of STAT3, a key component downstream of LIF and IL-6 receptors. LIF was apparently the major active factor in the conditioned media as the STAT3 response was almost completely neutralized by an anti-LIF antiserum. The presence of kininogen and kallikrein transcripts in neuronal cells but not in astrocytic cells indicates that neurons can produce bradykinin. Correspondingly, conditioned media from neuronal cells stimulated MAPKs in astrocytes in a HOE-140-sensitive manner. These studies demonstrate that paracrine signaling between neurons and astrocytes may involve ligands of Gq-coupled receptors and cytokines such as LIF.<\/jats:p>","DOI":"10.3390\/ijms252313079","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T06:24:44Z","timestamp":1733379884000},"page":"13079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of Bradykinin B2 Receptors in Astrocytes Stimulates the Release of Leukemia Inhibitory Factor for Autocrine and Paracrine Signaling"],"prefix":"10.3390","volume":"25","author":[{"given":"Ying","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"},{"name":"School of Public Health, Nantong University, Nantong City 226019, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yishan","family":"Gu","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony S. L.","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yung","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-7697","authenticated-orcid":false,"given":"Yung H.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"},{"name":"State Key Laboratory of Molecular Neuroscience, and the Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"},{"name":"Hong Kong Center for Neurodegenerative Diseases, InnoHK, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref_1","first-page":"1005","article-title":"Inflammation in Alzheimer\u2019s disease: Driving force, bystander or beneficial response?","volume":"12","year":"2006","journal-title":"Nat. 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