Antimicrobial Peptides in Acne Skins By Gay Wardle

Antimicrobial Peptides in Acne Skins

B y G a y W a r d l e

The Innate Immune System is the first defense system to protect against invading organisms, hence it’s very powerful presence in the epidermis. The skin is a host to normal microflora which is a colonization of bacteria that works with the innate immune system. Having a healthy microflora that works with the immune system protects the skin from invading pathogens that can cause harm to not only the skin, but the body itself. The second part of this defense system are the cells of the skin.

The keratinocytes and sebocytes also play a role in recognising invading pathogens by using pattern recognition receptors (PRC) such as toll-like receptors. Once this stimulation occurs, an amazing activation of chemical reactions takes place where the production of pro-inflammatory cytokines and anti-microbicidal peptides are released into extra cellular space. This communication between the keratinocyte cells, sebocytes and immune cells is crucial in defending the skin against harmful bacteria that causes skin infections.

The activation of pattern recognition receptors by keratinocyte cells and sebocytes is directly involved in the induction of antimicrobial peptides.

So, what are Antimicrobial Peptides?

Antimicrobial Peptides are crucial in maintaining the immunity of the skin by protecting against pathogens as well as maintaining healthy skin barrier homeostasis. Antimicrobial peptides are a very diverse group of cationic polypeptides that release a large spectrum of cytotoxic actions that destroy bacteria, viruses and fungi.

During the inflammatory stages, the keratinocyte cells are the main cellular sources of antimicrobial peptides and their levels are equivalent with the susceptibility of skin infections. AMPs contain 12–100 amino acids and are cationic and amphipathic in nature, which can interact with negatively charged membranes of microbes or host cells

They work with the immune system!

Antimicrobial peptides are part of the innate immune response, they defend against both gram negative and gram-positive bacteria as well as viruses, fungi and cancerous cells. There two main classifications of AMPs, one that targets internal processes and the other targeting external processes of micro-organisms. They work by first attacking the outer cell wall which is the lipid layer of a bacteria cell. Inside this lipid layer is what is know as the outer membrane proteins, these proteins are receptors for antimicrobial peptides which begins to break down the membrane proteins. The next phase is to act on the inner membrane which allows the peptides to enter into the cytoplasm of the cell. This part of the action of AMPs will alter and inhibit synthesis of the cell wall, nucleic acids, proteins and the enzymatic activity of the entire bacteria cell. A group of AMPs will then target the DNA of the bacteria by electrostatic attraction which will negatively charge the bonds in the nucleic acid backbone of DNA. This action inhibits all macromolecular synthesis stopping all of the protein synthesis in DNA. The last phase is to interfere with all of intracellular proteins. Once the DNA has been disrupted the AMPs will directly set about destroying all the proteins within the bacterial cell. Proline and arginine are proteins within cells, AMPs release a substance which binds to ribosome subunits that then inhibits protein synthesis. There we have complete destruction of the bacteria cell.

Acne & Antimicrobial Peptides

Antimicrobial peptides are found to be at very high levels in both acne and rosacea patients/ clients. These high levels of AMPs leads to the realisation that they are important mediators in acne skin infections. Both keratinocyte cells and sebocytes release large quantities of AMPs in response to bacterial proteins such as P.acnes.

These groups of molecule peptides attract other classes of inflammatory cells such as T-cells, monocytes and macrophages which when recruited increase the level of antimicrobial peptides hence increasing inflammation. Propionibacterium acnes is a commensal bacterium, which is involved in acne inflammation. Antimicrobial peptide named CEN1HC-Br, which was isolated and characterized form the green sea urchin, has been shown to possess broadspectrum antibacterial activity hence can reduce the inflammation.

Antimicrobial Peptides in Psoriasis

Psoriasis is a perfect example of an inflammatory condition in which the relationship between keratinocytes, which proliferates excessively and T lymphocyte, that maintains inflammation in the lesion. This represents the basis of a pathogenic process. The disease is actioned by the keratinocytes and T lymphocytes contributing to the development of the lesions. Psoriasis, a common skin disorder, is an autoimmune condition characterized by aberrant innate and adaptive immune responses, in which T cells, keratinocytes, and dendritic cells play a central role. Psoriasis can be triggered by injury, infections, and mechanical stimulation, especially in patients with a genetic predisposition. In this context, many active immune substances, including AMPs, rapidly increase in concentration in the local skin and initiate the maturation and activation of dendritic cells and T cells with excessive interleukin (IL)-17 expression, resulting in the infiltration of immune cells and an inflammatory cascade. The levels of AMPs, are higher in skin lesions and/or sera of psoriasis patients than in those of healthy patients. The immunoregulatory functions of AMPs in psoriasis have been highlighted in recent decades and there are many studies to support these findings. AMPs activate keratinocytes and innate immune cells, including neutrophils, macrophages, and dendrite cells mainly in a pattern recognition receptor (PRR)dependent manner. The activation leads to neutrophil and macrophage recruitment, neutrophil extracellular trap formation, and dendritic cell maturation.[ In addition, AMPs modulate adaptive immune responses in psoriasis by directly interacting with T cells as autoantigens.

Growing evidence supports the role of antimicrobial peptides and their receptors in the development of acne and psoriasis . It is important that we as clinicians have a good understanding of how the skin`s innate immune system functions so that we can effectively treat acne skin and inflammation. We are learning all the time about the impact antibiotics and medications have on the gut. We also need to understand the impact these medications have antimicrobial peptides and the affect that has on the immune system. The introduction in the cosmetic industry of pre biotic creams is very interesting, apart from assisting our skin`s own bacteria, there are further benefits to antimicrobial peptides that could be considered. There is growing concern with antimicrobial resistance occurring world wide with the uptake of anti-biotics yet, more and more we reach for anti-biotics as a quick fix to treat skin concerns and in most cases the end result is exacerbation of the condition.

Antimicrobial peptides are an integral part of the first-line defence of a host against pathogens, long term anti-biotics can impact on the immune systems own defence.