title: Modulation of the mRNAs encoding substance P and its receptor in rat macrophages by LPS.
abstract: Numerous soluble factors and their receptors contribute to the regulation of immune responses. An important area of investigation concerns defining the regulation of expression of such receptor/ligand pairs, since understanding such events are central in the quest to manipulate immune responses. Receptors for the neuropeptide, substance P, are present on a variety of leukocytes, and these receptor positive cells respond to in vitro stimulation with substance P in a variety of ways. Unfortunately, little is known about the regulation of expression of substance P or its receptor in leukocytes. Here we begin to address this question by examining the ability of macrophages to express mRNAs which encode substance P and its receptor. A radiolabeled oligonucleotide probe complementary to the mRNA which encodes substance P (i.e., preprotachykinin mRNA) hybridized to a 1.3 kb RNA species present in rat macrophages. In addition, the expression of this RNA could be upregulated 6 to 8 fold when macrophages were stimulated with LPS. The ability of macrophages to synthesize and secrete immunoreactive-substance P was demonstrated by incorporation of L-[35S]methionine into material from macrophage cultures which could be recognized by a monoclonal antisubstance antibody. Macrophage RNA of approximately 3.1 kb in size was capable of hybridizing with an oligonucleotide probe complementary to rat brain substance P receptors. In addition, this RNA could be upregulated when cells were exposed to LPS. Taken together, these studies suggest that the genes used by neuronal cells and macrophages to encode substance P and its receptor are similar if not identical.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, LA 70112.
authors.forename: K L
authors.initials: KL
authors.lastname: Bost
authors.forename: S A
authors.initials: SA
authors.lastname: Breeding
authors.forename: D W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D007941:Leukemia P388 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D015213:Neuroimmunomodulation; D011498:Protein Precursors / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D013373:Substance P / Q000235:genetics* / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D011498:Protein Precursors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P