OBJECTIVES: Chemokines are implicated in many diseases of the central nervous system (CNS). Although their primary role is to induce inflammation through the recruitment of leukocytes by their chemotactic activity, they may also have direct effects on neuronal cells. We evaluated the expression of CXCR1 and CXCR2 and investigated the effect of CXCR2 activation by the agonist MIP-2 (CXCL2) on primary cultured motor neurons. To specifically assess the role of CXCR2 in the neurotoxicity induced by MIP-2, we used the CXCR1/2 inhibitor reparixin and studied the effect of the chemokine on motor neuron cultures from CXCR2-deficient mice. METHODS: Primary motor neurons prepared from rat or mouse embryos were treated with MIP-2 and reparixin. Motor neuron viability and receptor expression were assessed by immunocytochemical techniques. RESULTS: Rat primary motor neurons expressed CXCR2 receptors and recombinant rat MIP-2 induced dose-dependent neurotoxicity. This neurotoxicity was counteracted by reparixin, a specific CXCR1/2 inhibitor, and was not observed in motor neurons from CXCR2-deficient mice. CONCLUSIONS: CXCR2 activation might directly contribute to motor neuron degeneration. Thus, chemokines acting on CXCR2, including IL-8, may have direct pathogenic effects in CNS diseases, independent of the induction of leukocyte migration. (c) 2008 S. Karger AG, Basel.
OBJECTIVES: Chemokines are implicated in many diseases of the central nervous system (CNS). Although their primary role is to induce inflammation through the recruitment of leukocytes by their chemotactic activity, they may also have direct effects on neuronal cells. We evaluated the expression of CXCR1 and CXCR2 and investigated the effect of CXCR2 activation by the agonist MIP-2 (CXCL2) on primary cultured motor neurons. To specifically assess the role of CXCR2 in the neurotoxicity induced by MIP-2, we used the CXCR1/2 inhibitor reparixin and studied the effect of the chemokine on motor neuron cultures from CXCR2-deficientmice. METHODS: Primary motor neurons prepared from rat or mouse embryos were treated with MIP-2 and reparixin. Motor neuron viability and receptor expression were assessed by immunocytochemical techniques. RESULTS:Rat primary motor neurons expressed CXCR2 receptors and recombinant ratMIP-2 induced dose-dependent neurotoxicity. This neurotoxicity was counteracted by reparixin, a specific CXCR1/2 inhibitor, and was not observed in motor neurons from CXCR2-deficientmice. CONCLUSIONS:CXCR2 activation might directly contribute to motor neuron degeneration. Thus, chemokines acting on CXCR2, including IL-8, may have direct pathogenic effects in CNS diseases, independent of the induction of leukocyte migration. (c) 2008 S. Karger AG, Basel.
Authors: Tao Zhang; Juhua Zhou; Gene Chi Wai Man; Kam Tong Leung; Bo Liang; Bo Xiao; Xinting Ma; Shaoyan Huang; Huaxiang Huang; Venkatesh L Hegde; Yin Zhong; Yanmin Li; Grace Wing Shan Kong; Alice Ka Wah Yiu; Joseph Kwong; Pak Cheung Ng; Bruce A Lessey; Prakash S Nagarkatti; Mitzi Nagarkatti; Chi Chiu Wang Journal: Eur J Immunol Date: 2018-03-13 Impact factor: 5.532
Authors: Michael Brines; Nimesh S A Patel; Pia Villa; Courtenay Brines; Tiziana Mennini; Massimiliano De Paola; Zubeyde Erbayraktar; Serhat Erbayraktar; Bruno Sepodes; Christoph Thiemermann; Pietro Ghezzi; Michael Yamin; Carla C Hand; Qiao-wen Xie; Thomas Coleman; Anthony Cerami Journal: Proc Natl Acad Sci U S A Date: 2008-08-01 Impact factor: 11.205