Antimicrobial peptides and the skin immune defense system

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.

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.