Scientific Explanation for Cathelicidin

Cathelicidin is an essential component of the immune system and is primarily known for its antimicrobial properties. This paper will provide a comprehensive overview of Cathelicidin, focusing on its structure, mechanisms of action, and significant role in inflammation control.

1. Structure and General Function of Cathelicidin

Cathelicidins are a family of host defence small proteins (HDPs) that are part of the innate immune system. In humans, the most well-known Cathelicidin is LL-37, derived from the hCAP18 precursor. Structurally, Cathelicidins consist of two parts: a conserved N-terminal cathelin domain and a variable C-terminal antimicrobial domain, which becomes active upon cleavage from its precursor.

The primary function of Cathelicidins is to defend the host against bacterial, viral, and fungal infections. They accomplish this by disrupting the membranes of invading pathogens, leading to cell lysis. In addition to their direct antimicrobial effects, Cathelicidins exhibit immune-modulatory properties, influencing both innate and adaptive immune responses. These proteins are found in various tissues, including the skin, respiratory tract, and digestive system, where they serve as first- line defenders against infection.1

2. Role of Cathelicidin in Immune Response

Cathelicidin's role in inflammation is multifaceted. While it acts as an antimicrobial proteins, it also influences inflammatory processes in both protective and pathological contexts. Cathelicidin can trigger or suppress inflammatory responses depending on the local microenvironment and the nature of the stimulus.

Cathelicidin anti-inflammatory properties are exhibited by modulating the immune response to prevent excessive inflammation. One of the key mechanisms through which Cathelicidin achieves this is by inhibiting the activation of nuclear factor-kappa B (NF-κB), a transcription factor that plays a central role in promoting inflammation by inducing the expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and IL-6.

Cathelicidin can also promote the differentiation of regulatory T cells (Tregs), which help maintain immune tolerance and prevent autoimmunity. Furthermore, Cathelicidin interacts with components of the adaptive immune system, such as dendritic cells, to promote a balanced immune response. This modulation is particularly important in tissues where an excessive inflammatory response can lead to tissue damage.2

3. Therapeutic Potential of Cathelicidin in Inflammatory Diseases

Due to its dual role in regulating inflammation, Cathelicidin is a promising target for developing new therapeutic strategies. Researchers are exploring ways to modulate Cathelicidin activity to treat chronic inflammatory conditions. In conditions characterized by excessive inflammation, such as psoriasis, strategies aimed at inhibiting Cathelicidin may help reduce disease severity. Conversely, in diseases where inflammation needs to be enhanced or better regulated, such as chronic infections or  ulcerative colitis, Cathelicidin-based therapies may help restore immune balance and promote healing.3

1 Alford MA, Baquir B, Santana FL, Haney EF and Hancock REW (2020) Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance. Front. Microbiol. 11:1902. doi: 10.3389/fmicb.2020.01902

2 Agier J, Efenberger M, Brzezińska-Błaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol. 2015;40(2):225-35. doi: 10.5114/ceji.2015.51359. Epub 2015 Aug 3. PMID: 26557038; PMCID: PMC4637384.

3 Wu, W., Wong, C., Li, Z. et al. Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders. Acta Pharmacol Sin 31, 1118–1122 (2010). https://doi.org/10.1038/aps.2010.117