Antimicrobial peptides and the skin immune defense system Jürgen Schauber, MD, Richard L. Gallo, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 122, Issue 2, Pages 261-266 (August 2008) DOI: 10.1016/j.jaci.2008.03.027 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Models for cell activation by cathelicidins. Multiple mechanisms have been proposed for cathelicidins to stimulate a cellular response. Responses are dependent on activation of G protein–coupled receptors and transactivation of the epidermal growth factor receptor or secondary to intracellular Ca2+ mobilization or a change in cell membrane function, leading to alterations in receptor responses. Finally, cathelicidins can influence the function of TLRs through both direct and indirect pathways. EGF-R, Epidermal growth factor receptor; IP-10, IFN-γ–inducible protein 10; MCP-1, monocyte chemoattractant protein 1; MIP3α, macrophage inflammatory protein 3α; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; STAT, signal transducer and activator of transcription. Journal of Allergy and Clinical Immunology 2008 122, 261-266DOI: (10.1016/j.jaci.2008.03.027) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Mechanisms of vitamin D3 activation and cathelicidin response. Extrarenal metabolism of vitamin D3 by keratinocytes provides a system for rapid control of cathelicidin expression. Activation of 25D3 to 1,25D3 requires 2 hydroxylation steps that occur sequentially in the liver and kidney. However, keratinocytes also express CYP27B1, a 1α-hydroxylase that activates 1,25D3. CYP27B1 expression in keratinocytes is controlled by danger signals during skin infection and tissue damage. Journal of Allergy and Clinical Immunology 2008 122, 261-266DOI: (10.1016/j.jaci.2008.03.027) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions