TY - JOUR
T1 - Cathelicidin antimicrobial peptides inhibit hyaluronan-induced cytokine release and modulate chronic allergic dermatitis
AU - Morioka, Yasuhide
AU - Yamasaki, Kenshi
AU - Leung, Donald
AU - Gallo, Richard L.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2008/9/15
Y1 - 2008/9/15
N2 - Antimicrobial peptides such as cathelicidins can modulate inflammation by interfering with TLR function. Small fragment hyaluronan (HA) is released following injury, and is an endogenous ligand for TLR4 as well as CD44. In this study, we examined the interactions of cathelicidin with HA. Cathelicidin inhibited HA-induced MIP-2 release from mouse bone marrow derived macrophages in a CD44 dependent manner but did not inhibit MALP2-induced MIP-2 release. This inhibitory activity was more potent than that of a peptide inhibitor of HA binding (Pep-1) and independent of Gi protein coupled or EGF-R signaling, both targets of cathelicidin inhibited HA-induced MIP-2 release. In assay of cell binding to HA, cathelicidins also significantly inhibited this process, suggesting that this antimicrobial peptide can interfere in other membrane binding events mediated by HA. The significance of this inhibition was demonstrated in a skin inflammation model induced by repeated application of 2,4-dinitrofluorobenzene. This induced an increase in HA at the site of application and was partially CD44 dependent. Camp-/- mice lacking cathelcidin demonstrated a large increase in ear swelling, cell infiltration, and MIP-2 expression compared with wild type mice. These results suggest that cathelicidin has antiinflammatory activity in skin that may be mediated in part by inhibition of HA-mediated processes.
AB - Antimicrobial peptides such as cathelicidins can modulate inflammation by interfering with TLR function. Small fragment hyaluronan (HA) is released following injury, and is an endogenous ligand for TLR4 as well as CD44. In this study, we examined the interactions of cathelicidin with HA. Cathelicidin inhibited HA-induced MIP-2 release from mouse bone marrow derived macrophages in a CD44 dependent manner but did not inhibit MALP2-induced MIP-2 release. This inhibitory activity was more potent than that of a peptide inhibitor of HA binding (Pep-1) and independent of Gi protein coupled or EGF-R signaling, both targets of cathelicidin inhibited HA-induced MIP-2 release. In assay of cell binding to HA, cathelicidins also significantly inhibited this process, suggesting that this antimicrobial peptide can interfere in other membrane binding events mediated by HA. The significance of this inhibition was demonstrated in a skin inflammation model induced by repeated application of 2,4-dinitrofluorobenzene. This induced an increase in HA at the site of application and was partially CD44 dependent. Camp-/- mice lacking cathelcidin demonstrated a large increase in ear swelling, cell infiltration, and MIP-2 expression compared with wild type mice. These results suggest that cathelicidin has antiinflammatory activity in skin that may be mediated in part by inhibition of HA-mediated processes.
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U2 - 10.4049/jimmunol.181.6.3915
DO - 10.4049/jimmunol.181.6.3915
M3 - Article
C2 - 18768846
AN - SCOPUS:56149103147
VL - 181
SP - 3915
EP - 3922
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -