Toll-like receptors (TLRs) play an important role in acne. It has been shown that P. acnes bacteria stimulate the Toll-like 2 (TLR-2) receptor to produce cytokines that lead to inflammation and acne. A growing body of research has uncovered several novel acne treatment approaches that work by blocking the expression of TLRs to inhibit the skin’s inflammatory response associated with acne lesions.
Continued research is being done to perfect these treatment options. Understanding the link between TLRs and inflammation is a crucial aspect of properly prescribing and managing acne treatments that are centered on inhibiting TLR-2 expression.
What Are Toll-Like Receptors?
Toll-like receptors are a group of glycoproteins that “turn on” the body’s immune response when certain potentially harmful microorganisms are detected. There are ten known TLRs in humans that are able to recognize a wide range of proteins, lipids, and nucleic acids that may induce an inflammatory response. When one of these harmful molecules is detected, TLRs work by triggering the production of inflammatory cytokines.
TLR expression can widely vary, depending on the specific cell type in which it is located. In the human epidermis, keratinocytes and Langerhans cells are the most important cells associated with TLR expression. Keratinocytes can express TLRs 1 through 6, while Langerhans cells can express all TLRs. Other cells in human skin, including dermal monocytes and macrophages, lymphocytes, mast cells, fibroblast cells, and adipocytes, can also play a role in TLR expression.
In some cases, the stimulation of TLRs is an important component of treatment for conditions such as viral infections or skin cancer. In these instances, an inflammatory response is required for treatment. When managing conditions such as acne, atopic dermatitis, psoriasis, and rheumatoid arthritis, TLRs can be inhibited to reduce inflammation and therefore symptom flare-ups of these inflammatory conditions.
Toll-Like Receptors and Acne
Acne is largely caused by Propionibacterium acnes, now referred to as Cutibacterium acnes, bacteria, which triggers an inflammatory response in the skin. Large amounts of TLR-2 have been found on skin cells affected by active acne lesions. It has also been found that larger numbers of cells expressing TLR-2 equated to more severe acne. P. acnes may also activate TLR-4. Researchers have begun to explore topical treatment options to inhibit the expression of TLR-2 and TLR-4 and therefore inhibit the inflammatory response related to acne and other skin conditions.
Topical retinoids, nicotinamide, and zinc have been shown to inhibit TLR-2 expression and therefore help control acne.
Adapalene is a topical retinoid that binds to receptors that inhibit TLR-2 expression. In this way, retinoids reduce inflammation associated with acne, which is one important way they are able to treat this common skin disorder. Studies have shown that other topical vitamin A derivatives, such as all-trans retinoic acid, share this same TLR-2 inhibiting effect.
Nicotinamide is a vitamin B3 derivative that inhibits the production of inflammatory cytokines. Studies show that nicotinamide is an effective topical treatment for acne, due to its anti-inflammatory effects.
Zinc has long been known to have anti-inflammatory properties, and recent evidence found that zinc salts inhibit inflammation by blocking TLR-2 expression.
A Potential TLR-2 Inhibitor
We know that C. acnes bacteria can be controlled by certain beneficial bacteria, including Enterococcus faecalis SL5, which produces an antimicrobial peptide called CBT-SL5. This peptide may be an effective topical treatment for acne by targeting P. acnes bacteria and preventing it from binding to TLR-2 receptors. However, more research is needed to determine the exact pathways necessary for CBT-SL5 to block inflammation caused by P. acnes bacteria.
Acne is the single most common skin disorder, yet many of the current treatments are flawed. The widespread use of antibiotics has created problems with antibiotic resistance, and bacteria-killing ingredients like benzoyl peroxide are not well-tolerated for some skin types. Benzoyl peroxide and blue light therapy may also accelerate skin aging.
Therefore, further research into the relationship between TLR-2 and acne could yield exciting new approaches to the treatment of acne and other inflammatory skin conditions. Further, the topical treatments that are now known to block TLR-2 expression and therefore manage acne and inflammation are safe and come with very few adverse effects.
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