**4. Spotting differences between normal and inflammatory keratinocyte proteome pattern**

The skin proteome has been the target of intense research in the last years, hence human epidermal keratinocytes, dermal fibroblasts, human epidermis, were characterized regarding their proteome pattern [25–28]. Ong et al. furthered these studies and published the specific proteomic markers in the normal skin and in the one subjected to inflammatory processes. In normal skin, there are several proteins that were reported as having high expression, such as carbonic anhydrase, HSP27, gelsolin, prostate binding protein, MnSOD, a1-antitrypsin, keratin 1 and keratin 10. On the contrary, in keloid scars, there is a low expression or even absence of carbonic anhydrase proving the maintenance of local inflammatory status of the skin. In this manner, the inflamed skin shows intense expression of the proliferative keratin 16 [29]. Other proteomic markers are found to be increased in the inflamed keratinocytes in comparison to normal skin, such as S100A4 /A8 /A9 /A10 [30]. The over-expression of this protein family was found also in other inflammatory diseases as well as in psoriatic keratinocytes [31, 32]. Over-expression of mast cell proteins was also found in inflamed keratinocytes, namely activation proteins, mast cell b-tryptase, and so on [29]. Mast cell b-tryptase can further induce tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin-1b (IL-1b) upregulating and also collagen type I and fibronectin expression [33]. Another pro-inflammatory protein found overexpressed in inflammatory keratinocytes, macrophage migration inhibitory factor (MIF), can be involved in the amplification of the inflammatory responses developed during wound healing.

Components of the skin's extracellular matrix (ECM), like the small leucine-rich proteoglycan family members, asporin and decorin, are inhibited by direct binding of the transforming growth factor β (TGF-β) activity [34]. In inflamed keratinocytes, high asporin expression was reported and this overexpression is probably due to the inflammatory response in human dermal wounds [29].

Differences in the proteomic pattern between normal and inflammatory keratinocytes reside in several important classes of overexpressed proteins. These are appending to the inflammation, tumor suppression, and fibrosis processes. The dynamic expression of these proteins can be important in depicting the therapeutic target potential.
