Substance P regulates macrophage inflammatory protein 3alpha/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells.

Abstract

Although substance P (SP), a potent proinflammatory peptide, is involved in inflammation and immune responses, the effect of SP on the expression of macrophage inflammatory protein 3alpha[MIP-3alpha, chemokine C-C ligand 20 (CCL20)] in periodontal ligament (PDL) cells is unknown. Equally enigmatic is the link between SP, the stress protein heme oxygenase-1 (HO-1), and CCL20 production. We investigated whether SP induces the release of chemokine CCL20 from immortalized PDL (IPDL) cells, and further clarify SP-mediated pathways. We also examined the relationship between HO-1 and CCL20 by treating PDL cells with SP. Incubating IPDL cells with SP increased expression of CCL20 mRNA and CCL20 protein in a dose-time-dependent manner. Highly selective p38 and extracellular-regulated kinase 1/2 (ERK1/2) inhibitors abrogated SP-induced expression of CCL20 in IPDL cells. SP is also responsible for initiating phosphorylation of IkappaB, degradation of IkappaB and activation of nuclear factor (NF)-kappaB. SP induced expression of HO-1 in both a concentration- and time-dependent manner, and CCL20 reflected similar patterns. The inductive effects of SP on HO-1 and CCL20 were enhanced by HO-1 inducer hemin and the membrane-permeable guanosine 3',5'-monophosphate (cGMP) analogue 8-bromo-cGMP. Conversely, this pathway was inhibited by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase, 1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one (ODQ). We report herein the pathway that connects SP along with other modulators of neuroimmunoregulation to the induction of HO-1 and the inflammatory mediator macrophage inflammatory protein (MIP)-3alpha/CCL20 in IPDL cells, which play an important role in the development of periodontitis or inflammation during orthodontic tooth movement.

• Authors: S-K Lee, S-H Pi, S-H Kim, K-S Min, H-J Lee, H-S Chang, K-H Kang, H-R Kim, H-I Shin, S-K Lee, E-C Kim
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 150 Issue 3 Pg. 567-75 (Dec 2007) ISSN: 1365-2249 [Electronic] England
• PMID: 17924972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL20 protein, human
• Chemokine CCL20
• Cytokines
• I-kappa B Proteins
• Inflammation Mediators
• Macrophage Inflammatory Proteins
• NF-kappa B
• NFKBIA protein, human
• RNA, Messenger
• NF-KappaB Inhibitor alpha
• Substance P
• Heme Oxygenase-1

Topics

• Cell Death (drug effects)
• Cell Line, Transformed
• Cell Transformation, Viral
• Cells, Cultured
• Chemokine CCL20 (genetics, metabolism)
• Cytokines (pharmacology)
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (metabolism, physiology)
• Humans
• I-kappa B Proteins (metabolism)
• Inflammation Mediators (pharmacology)
• Macrophage Inflammatory Proteins (genetics, metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (physiology)
• Periodontal Ligament (cytology, drug effects, metabolism)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics)
• Substance P (pharmacology)