Role of hypoxia-inducible factor-1  in hypoxia-induced expressions of IL-8, MMP-1 and MMP-3 in rheumatoid fibroblast-like synoviocytes

Abstract

Hypoxia-induced MMP-3 expression is exclusively regulated by HIF-1alpha, and hypoxia-induced MMP-1 or IL-8 expression appears to have salvage pathways other than the HIF-1alpha pathway. Together, these data provide new insight regarding the mechanism by which hypoxia participates in joint inflammation and destruction in RA.

Redox Control of the Senescence Regulator Interleukin-1α and the Secretory Phenotype

“…The feasibility of this approach was demonstrated using H 2 O 2 -specific antioxidants, showing they can dramatically reduce SA IL-1␣ expression and ultimately prevent expression of the downstream SASP factors IL-6 and IL-8. Interestingly, IL-8 expression is not sensitive to low O 2 exposure, which is likely explained by the fact that IL-8 expression can be regulated by hypoxia-inducible factor-1␣ (37)(38)(39), which is stabilized in the 0.1-4% O 2 range (40). Although antioxidants limit the expression of IL-1␣, they may also prevent the Ca 2ϩ -dependent processing of this factor.…”

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

“…F2 could inhibit the hypoxia-simulated tumor angiogenesis and cell invasion in vitro in a HIF-1α-dependent manner, and MMP-2 may be the key protein participating in the inhibitory effect of F2 on cell invasion because it could be involved in the breakdown of the extracellular matrix (31). However, there are other proteins participating in the hypoxia-induced tumor invasion, such as CXC chemokine receptor 4 (CXCR4) and interleukin-8 (IL-8) (38,39). Accordingly, additional studies are underway to identify the associated genes that are directly or indirectly involved in the inhibitory effect of F2 on tumor cell invasion in response to hypoxia and/or HIF-1α overexpression.…”

cAMP-response Element-binding Protein (CREB) and NF-κB Transcription Factors Are Activated during Prolonged Hypoxia and Cooperatively Regulate the Induction of Matrix Metalloproteinase MMP1

“…Previous reports indicate that NF-B, p38, and JNK pathways are involved in MMP1 expression by cytokine stimulation in fibroblast or chondrocytes (10,11). It was also reported that induction of MMP1 is mediated by HIF-1 during hypoxia in fibroblasts (12,13) or by HIF-2 in chondrocytes upon IL-1␤ stimulation (14). Although HIF is a key regulator of the hypoxic response, it remains unclear if MMP1 is induced by these factors during prolonged hypoxia or if any other factor(s) is involved in MMP1 induction.…”