VIP and PACAP down-regulate CXCL10 (IP-10) and up-regulate CCL22 (MDC) in spleen cells

J Neuroimmunol. 2002 Dec;133(1-2):81-94. doi: 10.1016/s0165-5728(02)00365-x.

Abstract

The immunoregulatory neuropeptides VIP and PACAP favor Th2-type immune responses. Antigen-stimulated Th2 cells produce VIP, VIP/PACAP induce Th2 cytokine responses, and promote the preferential survival of Th2 effectors. In this study, we investigate the effects of VIP/PACAP on two chemokines, i.e. CXCL10 (IP-10) acting on CXCR3 expressed on activated Th1 cells, and CCL22 (MDC) acting on CCR4 and 8 expressed on activated Th2 cells. VIP and PACAP down-regulate CXCL10, and up-regulate CCL22 in vivo and in vitro. The effects on the two chemokines appear to be different in mechanistic terms. The fact that VIP/PACAP might promote the directed migration of Th2 cells adds a new dimension to their participation in the Th2 auto-regulatory loop.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Chemokine CCL22
  • Chemokine CXCL10
  • Chemokines, CC / immunology*
  • Chemokines, CXC / genetics
  • Chemokines, CXC / immunology*
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neuropeptides / immunology*
  • Neuropeptides / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Spleen / cytology
  • Spleen / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology
  • Vasoactive Intestinal Peptide / immunology*
  • Vasoactive Intestinal Peptide / pharmacology

Substances

  • Adcyap1 protein, mouse
  • Ccl22 protein, mouse
  • Chemokine CCL22
  • Chemokine CXCL10
  • Chemokines, CC
  • Chemokines, CXC
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • RNA, Messenger
  • Receptors, Cell Surface
  • Vasoactive Intestinal Peptide