title: Human neuronal cells (NT2-N) express functional substance P and neurokinin-1 receptor coupled to MIP-1 beta expression.
abstract: Substance P (SP), the most extensively studied and potent member of the tachykinin family, is a major modulator of inflammation and immunomodulatory activities within the central and peripheral nervous systems. We have examined the gene expression of SP and its receptor in a human neuronal cell line (NT2-N). Using reverse transcribed polymerase chain reaction (RT-PCR), the four isoforms of preprotachykinin-A gene transcripts (alpha, beta, gamma, and delta) were detected in the NT2-N. We also identified the presence of mRNA for neurokinin-1 receptor (NK-1R), a primary receptor for SP, in the NT2-N cells. Concomitant with NT2 cell differentiation into neurons, SP and NK-1R mRNA expression increased consistently. Intracellular SP and cell membrane NK-1R immunoreactivity were all observed in NT2-N cells. Most importantly, we demonstrated that SP and NK-1R presented in NT2-N cells are functionally involved in the regulation of macrophage inflammatory protein 1 beta (MIP-1beta), an important beta-chemokine participating in the activation and directional migration of immune cells to sites of central nervous systems (CNS) inflammation. Thus, SP and its receptor may play an important role in modulation of neuronal functions related to regulation of immune activities within the CNS. The NT2-N cell line is well suited for in vitro investigations of the SP-NK-1R pathway in immune responses and inflammation in the CNS.
authors.affiliation: Division of Immunologic and Infectious Diseases, Joseph Stokes, Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: David E
authors.initials: DE
authors.lastname: Pleasure
authors.forename: Jianping
authors.initials: J
authors.lastname: Lai
authors.forename: Changjiang
authors.initials: C
authors.lastname: Guo
authors.forename: Peter
authors.initials: P
authors.lastname: Bannerman
authors.forename: Marge
authors.initials: M
authors.lastname: Williams
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D002478:Cells, Cultured; D054407:Chemokine CCL4; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000096:biosynthesis*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis* / Q000502:physiology; D013373:Substance P / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology
chemical_list: D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D018040:Receptors, Neurokinin-1; D013373:Substance P