Skin is exposed to the external environment that brings with it daily aggressions such as UV light, chemicals, pollution, temperature, etc. These aggressions can create skin irritation, especially in sensitive skin individuals, leading to itching and discomfort. Moreover, in the long-term, irritation leads to skin damage and premature aging as a result of elastosis and matrix degradation.1-3 It is therefore important to stop skin irritation rapidly to not only reduce skin discomfort, but also avoid further skin damage.
Skin irritation is sustained by a cross-talk mechanism between a keratinocyte in the epidermis layer and the infiltrating immune cell, e.g. T lymphocytes. This cross-talk creates an amplification loop that leads to overreaction and escalates the inflammatory process with consequent skin erythema and irritation. Under these circumstances, the skin is unbalanced and requires re-balancing.
NF-κB and JAK/STAT Pathways
The NF-κB and JAK/STAT signaling pathways are both dramatically amplified in dermatological conditions and play substantial roles in sustaining skin irritation.4 In the NF-κB pathway, a cytokine receptor expressed on the cell membrane of the keratinocyte will recognize cytokine ligands produced by skin-infiltrating immune cells, thus triggering the release in the cytoplasm of the NF-κB unit, which is normally sequestered by a family of inhibitory proteins known as inhibitors of NF-κB (IκBs). The signaling pathway from the receptor will lead to the liberation and nuclear accumulation of NF-κB, in turn activating the transcription of pro-inflammatory molecules such as cytokines and chemokines.5, 6