LL-37, a natural antimicrobial peptide, can make human mast cells release chemicals that cause allergy‑type reactions. However, when the cells are also exposed to TLR2‑activating molecules (like peptidoglycan or Pam3CSK4), the allergic response is dampened, and the cells shift toward a more general immune‑defense mode. The study was done in a lab cell line, not in people, so the findings are early‑stage.

The sole and endogenous anti-microbial peptide LL-37 is a significant effector molecule in the innate host defense system. Apart from its broadly direct anti-microbial activity, the peptide also activates mast cell in respect of allergic diseases and inflammation. On the other hand, mast cell can be activated by Toll-like receptors (TLRs) which are at the center of innate immunity. It was the aim of the study to illustrate the modulatory effect of TLR2 ligands peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4) on LL-37 induced LAD2 cells (a human mast cell line) activation. LL-37 induced LAD2 cells degranulation and the release of IL-8. TLR2 ligands didn't induce LAD2 cells degranulation, but triggered the release of IL-8. Incubation with PGN or Pam3CSK4 significantly suppressed LL-37-induced degranulation through inhibition of calcium mobilization from LAD2 cells. Similarly, the release of IL-8 was inhibited when LAD2 cells were co-stimulated with TLR2 ligands and LL-37. Studies with inhibitors of key enzymes involved in mast cell signaling indicated that the release of IL-8 induced by TLR2 ligands and LL-37 involved the activation of the PI3K, ERK, JNK and calcineurin signaling pathways. In contrast, p38 activation down-regulated the release of IL-8 induced by TLR2 ligands and LL-37. Taken together, these observations suggest that activation of human mast cells by LL-37 could be modified by TLR2 ligands and the function of human mast cells could be switched from allergic reactions to innate immune response.