Metalloproteinases and tissue inhibitor of metalloproteinases in mesothelial cells. Cellular differentiation influences expression.

Abstract

Mesothelial cells play a critical role in the remodeling process that follows serosal injury. Although mesothelial cells are known to synthesize a variety of extracellular matrix components including types I, III, and IV collagens, their potential to participate in matrix degradation has not been explored. We now report that human pleural and peritoneal mesothelial cells express interstitial collagenase, 72-and 92-kD gelatinases (type IV collagenases), and the counterregulatory tissue inhibitor of metalloproteinases (TIMP). Our initial characterization of the mesothelial cell metalloenzymes and TIMP has revealed: (a) they are likely identical to corresponding molecules secreted by other human cells; (b) they are secreted rather than stored in an intracellular pool; (c) a primary site of regulation occurs at a pretranslational level; (d) phorbol myristate acetate, via activation of protein kinase C, upregulates expression of collagenase, 92-kD gelatinase, and TIMP, but has no effect on expression of 72-kD gelatinase; and (e) lipopolysaccharide fails to upregulate the biosynthesis of either metalloproteinases or TIMP. Of particular interest is the observation that the state of cellular differentiation has a striking influence on the expression of metalloenzymes and TIMP, such that epithelioid cells display a more matrix-degradative phenotype (increased 92-kD gelatinase and decreased TIMP) than their fibroblastoid counterparts. We speculate that mesothelial cells directly participate in the extracellular matrix turnover that follows serosal injury via elaboration of metalloproteinases and TIMP. Additionally, the reactive cuboidal mesothelium which is characteristic of the early response to serosal injury may manifest a matrix-degradative phenotype favoring normal repair rather than fibrosis. (J. Clin. Invest. 1993. 91:1792-1799

Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions

“…Thus, they considered their expression in pleural fluid to be a constitutive characteristic of the resident mesothelial cells [1,2]. The in vitro studies by MARSHALL et al [21] demonstrated that mesothelial cells constitutively express MMP-2 and TIMP. MMPs and TIMPs in plasma and pleural fluid in empyema and complicated parapneumonic pleural effusions In this group of effusions, higher levels of MMPs and TIMPs were found in pleural fluid than in plasma, and no correlation was found between the concentrations in the two samples.…”

Pleurodesis induced by intrapleural injection of silver nitrate or talc in rabbits: can it be used in humans?

“…The degree of the lesion is important, because it is probably proportional to the effectiveness of pleurodesis and to the capacity of the mesothelial cells to secrete or break down collagen (14) . It has been suggested that the duration, extension, and intensity of the inflammation may influence the final result, on the grounds that, in rabbits, pleurodesis produced by talc is inhibited by the use of corticoids (15) and by intrapleural administration of tumor necrosis factor (TNF)-blocking antibodies (16) .…”

Η Επίδραση Των Μεταλλοπρωτεϊνασών Στη Διαπερατότητα Του Υπεζωκότα

“…Il-1β η παραγωγή και έκκριση TIMP-1 στην υπεζωκοτική κοιλότητα αυξάνεται [152,153]. Αναστέλλει όλες τις ΜΜPs, εκτός από τις διαμεμβρανικές MMPs (ΜΤ-ΜΜPs).…”

“…Στην εργασία των Marshall και συν., οι συγγραφείς μελέτησαν την έκφραση και έκκριση των MMP2 και MMP9 από τα μεσοθηλιακά κύτταρα αλλά δεν εξέτασαν την κατεύθυνση της έκκρισης των ενζύμων αυτών, δηλαδή εάν αυτή γίνεται προς την κορυφαία ή την πλαγιοβασική επιφάνεια των μεσοθηλιακών κυττάρων [152].…”

“…Η MMP2 εκφράζεται και εκκρίνεται υπό βασικές συνθήκες στην υπεζωκοτική κοιλότητα από τα μεσοθηλιακά κύτταρα [152]. Στα εξιδρώματα τα υψηλά επίπεδα MMP2 μπορεί να οφείλονται σε αυξημένη έκφραση ως αποτέλεσμα διέγερσης των μεσοθηλιακών κυττάρων από κυτταροκίνες αλλά και κύτταρα, όπως τα μονοκύτταρα, μπορεί να συμβάλλουν στην απελευθέρωση υψηλών επιπέδων MMP2 [153].…”