APC0576 decreases production of pro-inflammatory chemokine and extracellular matrix by human Tenon's capsule fibroblasts.
OBJECTIVE
To control intraocular pressure in patients treated by trabeculectomy, progressive inflammation, fibroblast proliferation, and the enhanced expression of extracellular matrix (ECM), causes of scar formation at the bleb, must be prevented. Using human Tenon's capsule fibroblasts (TCFs), we examined the effect of APC0576, a suppressor of NF-kappaB-dependent gene activation of human vascular endothelial cells that does not adversely affect cell viability, on the production of pro-inflammatory chemokine and ECM. Its effect on TCF proliferation was also assessed.


METHODS
Enzyme-linked immunosorbent assay was used to detect the pro-inflammatory cytokines IL-8 and MCP-1 in the supernatant of TCFs stimulated with IL-1alpha in the presence or absence of APCO576 and ECM proteins, COOH-terminal peptide of type I procollagen (PIP), fibronectin (FN), and laminin (LN) in supernatants and lysates of TCFs stimulated with IL-1alpha or TGF-beta. The proliferative response of IL-1alpha-stimulated TCFs was examined using the SF formazan solution reaction.


RESULTS
APC0576 significantly suppressed the production by TCFs of IL-8 (p<0.0001), MCP-1(p<0.0001), PIP (supernatants: p<0.0001, cell lysates: p<0.0001), LN (supernatants: p<0.0001, lysates: p<0.0001), and FN (supernatants: p<0.0001, lysates: p<0.0001) as well as their proliferation (p<0.0001).


CONCLUSIONS
APC0576 suppressed pro-inflammatory chemokine and ECM production in TCFs as well as their proliferation. It may represent a novel candidate for the postoperative management of patients treated by trabeculectomy.
Naruse
Shigeta
S
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kawaramachi Kamigyo-ku, Kyoto 602-0841, Japan. snaruse@ophth.kpu-m.ac.jp
Yamada
Jun
J
Hamuro
Junji
J
Kobayashi
Tsuyoshi
T
Mori
Kazuhiko
K
Kinoshita
Shigeru
S
D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D003521:Cyclopropanes / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects*; D005123:Eye / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D014130:Trabeculectomy; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
C457774:5-((2,2-dimethylcyclopropanecarbonyl)amino)-2-(4-((2,2-dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine; D018925:Chemokines; D003521:Cyclopropanes; D007375:Interleukin-1; D011725:Pyridines; D016212:Transforming Growth Factor beta