title: Anti-inflammatory effects of the nicotinergic peptides SLURP-1 and SLURP-2 on human intestinal epithelial cells and immunocytes.
abstract: A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD) is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2--the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC) and immunocytes--can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFN γ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1 β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1 β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγ R in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD.
authors.affiliation: Department of Dermatology, University of California, 134 Sprague Hall, Irvine, CA 92697, USA.
authors.forename: Alex I
authors.initials: AI
authors.lastname: Chernyavsky
authors.affiliation: Department of Dermatology, University of California, 134 Sprague Hall, Irvine, CA 92697, USA.
authors.forename: Valentin
authors.initials: V
authors.lastname: Galitovskiy
authors.affiliation: National Cancer Institute, Kiev 03022, Ukraine.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Shchepotin
authors.affiliation: Department of Dermatology, University of California, 134 Sprague Hall, Irvine, CA 92697, USA ; Department of Biological Chemistry, University of California, 134 Sprague Hall, Irvine, CA 92697, USA ; Institute for Immunology, University of California, 134 Sprague Hall, Irvine, CA 92697, USA.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grando
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000950:Antigens, Ly / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; D000950:Antigens, Ly; D016207:Cytokines; D058851:GPI-Linked Proteins; C485626:LYNX1 protein, human; D009479:Neuropeptides; D011994:Recombinant Proteins; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator