Assessment of Selected Matrix Metalloproteinases (MMPs) and Correlation with Cytokines in Psoriatic Patients

Abstract

Metalloproteinases (MMPs) and cytokines have a great impact on the pathogenesis of psoriasis. Cytokines, as key mediators of inflammation and autoimmune processes, play a crucial role in the regulation of MMP expression in different cell types. Parallel, MMPs have an influence on cytokine production. This interaction was not well recognized in psoriatic patients. Our study is aimed at assessing the selected serum MMP levels and their correlations with cytokine levels in the serum of psoriatic patients. We observed a significantly elevated level of pro-MMP-1 and MMP-9 in psoriatic patients’ serum in comparison to the control group. We did not observe any statistically significant differences of MMP-3 and pro-MMP-10 between the psoriatic patients and the control group. We did not observe any statistically significant differences in all the studied MMP levels between the patients with and without psoriatic arthritis (PsA). MMP-3 level correlated positively with proinflammatory cytokines, i.e., IL-12p/70, IL-17A, and TNF-α as well as MMP-3 and pro MMP-1 correlated positively with IL-4 in the psoriatic patients. In the control group, a positive correlation between pro-MMP-1 and TNF-α was found. These results confirm MMPs and Th1 and Th17 cytokine interaction in the inflammatory regulation in psoriasis.

Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery

“…According to previous work, such MMP-responsive linkers should be readily cleaved by a range of MMPs, including MMP-9 and MMP-7. , A range of other proteases are also present in skin, including human leukocyte elastase, proteinase 3, and cathepsin G. A cleavage site specificity study performed on tropoelastin showed, however, that these proteases do not have a high preference for Leu in P1′, Pro in P3, or Gly in P3′, hence no interference from such enzymes to the performance of the presently investigated system is expected. To provide a proof of concept, we chose to add activated MMP-9 in a concentration of 80 nM, which represents a physiologically relevant concentration of collectively acting subtypes of MMPs in the dermis during inflammation in vivo . Due to autocatalysis, MMP-9 activity is present only transiently .…”

“…To provide a proof of concept, we chose to add activated MMP-9 in a concentration of 80 nM, which represents a physiologically relevant concentration of collectively acting subtypes of MMPs in the dermis during inflammation in vivo. 27 Due to autocatalysis, MMP-9 activity is present only transiently. 51 To mimic the inflammatory relapsing course seen for many skin diseases, MMP-9 was therefore added multiple times.…”

“…Microparticles were prepared using inverse suspension photopolymerization and characterized comprehensively with respect to size, morphology, zeta potential, mechanical properties, susceptibility toward enzymatic degradation by MMP-9, in vitro drug release, and cytotoxicity toward skin fibroblasts. MMP-9 was specifically chosen as a relevant stimulus because of its significant upregulation in inflamed skin compared to that in healthy skin, 27 as well as the high abundance of MMP-9 found in a skin inflammation mouse model treated with topical applied imiquimod (unpublished). Crosslinked spherical microparticles loaded with TC were readily dispensed through 27G needles and exhibited Young's moduli comparable to that of dermis when hydrated.…”

The Mind Body Connection in Dermatologic Conditions: A Literature Review

“…106 There has been further evidence of increased expression of MMP genes in human psoriatic lesions and human keratinocytes cultured with IL-17. 107,108 Specifically, elevated levels of MMP-9 and pro-MMP-1 levels were observed in patients' serum, and MMP-3 was further correlated with cytokines IL-4, IL-17A, TNF-α in psoriatic patients. 107,109,110 In addition, the HPA axis may be implicated in psoriasis.…”

“…107,108 Specifically, elevated levels of MMP-9 and pro-MMP-1 levels were observed in patients' serum, and MMP-3 was further correlated with cytokines IL-4, IL-17A, TNF-α in psoriatic patients. 107,109,110 In addition, the HPA axis may be implicated in psoriasis. 104 CRH has been shown to be involved in a number of cutaneous roles including stimulation of IL-6 and IL-11 production and activation of pro-inflammatory complex protein of NF-kβ, ultimately priming keratinocytes for a proinflammatory state.…”