Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!

Gaber, Timo; Dziurla, René; Tripmacher, Robert; Burmester, Gerd R.; Buttgereit, Frank

doi:10.1136/ard.2004.031641

Cited by 141 publications

(139 citation statements)

References 107 publications

(73 reference statements)

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“…Inflammation as a bioenergetically highly active process is associated with a reduction of oxygen availability [7,8]. However, it is not only for this reason that one can assume the presence of bioenergetically restricted conditions in the initial FH; additionally, the simple existence of interrupted blood vessels will lead to an insufficient oxygen supply.…”

Section: Discussionmentioning

confidence: 99%

“…Innate immune cells and CD4 + T cells adapt well to energy insufficiencies in that they are assumed to prevail in FHs [5,44]. The hypoxia-inducible factor (HIF) plays an important role as a regulator to adapt to oxygen depletion [7]. HIF and its regulation mechanisms are crucial for the functions of both a congenital and an adaptive immune system [5,8].…”

Section: Introductionmentioning

confidence: 99%

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Human Early Fracture Hematoma Is Characterized by Inflammation and Hypoxia

Kolar

Gaber

Perka

et al. 2011

Clinical Orthopaedics &Amp; Related Research

159

174

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Early Fracture Hematoma Is Characterized by Inflammation and Hypoxia

Kolar

Gaber

Perka

et al. 2011

Clinical Orthopaedics &Amp; Related Research

159

174

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show abstract

“…32 Hypoxia is present in synovial fluid of knee with synovitis and rheumatoid arthritis. 23,33,34 In a related study in our lab, we have found that the acute ACL injury induces a chronic hypoxic microenvironment in the synovial fluid (manuscript in preparation). The molecular responses to hypoxia include accumulation of active HIF-1ab heterodimers in cell nuclei and induction of many genes.…”

Section: Discussionmentioning

confidence: 99%

“…Many physical (mechanical stress, heat, and low pH), biochemical factors (cytokines, hormones, growth factors), and pathophysiological conditions induce HIF-1a. 23,24 Many studies signify that constituents of microenvironment after injury affects the overall pathophysiology and repair of affected intra-articular tissues and needs to be studied. Moreover, MMP-2 production in response to induced HIF-1a has not been elucidated in the injured ACL.…”

mentioning

confidence: 99%

Combined effects of TNF‐α, IL‐1β, and HIF‐1α on MMP‐2 production in ACL fibroblasts under mechanical stretch: An in vitro study

Wang

Tang

Xue

et al. 2011

Journal Orthopaedic Research

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ABSTRACT:The dynamics between inflammatory factors, mechanical stress, and healing factors, in an intra-articular joint, are very complex after injury. Injury to intra-articular tissue [anterior cruciate ligament (ACL), synovium] results in hypoxia, accumulation of various pro-inflammatory factors, cytokines, and metalloproteases. Although the presence of increased amounts of matrix-metalloproteinases (MMP) in the joint fluid after knee injury is considered the key factor for ACL poor healing ability; however, the exact role of collective participants of the joint fluid on MMP-2 activity and production has not been fully studied yet. To investigate the combined effects of mechanical injury, inflammation and hypoxia induced factor-1a (HIF-1a) on induction of MMP-2; we mimicked the microenvironment of joint cavity after ACL injury. The results show that TNF-a and IL-1b elevate the activity of MMP-2 in a dose-and time-dependent manner. In addition, mechanical stretch further enhances the MMP-2 protein levels with TNF-a, IL-1b, and their mixture. CoCl 2 -induced HIF-1a (100 and 500 mM) also increases the levels and activity of MMP-2. Mechanical stretch has a strong additional effect on MMP-2 production with HIF-1a. Our results conclude that mechanical injury, HIF-1a and inflammatory factors collectively induce increased MMP-2 production in ACL fibroblasts, which was inhibited by NF-kB pathway inhibitor . ß

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“…Compared to wild-type mice, HIF-1α myeloid-null animals have less skin redness and edema after irritation with detergent solution, and greatly diminished joint swelling and cartilage destruction in a passive serum-induced arthritis model [7]. A role for HIF-1α in chronic inflammatory diseases such as rheumatoid arthritis and atherosclerosis is further corroborated by elevated levels of the transcription factor in biopsies of primary lesions of patients [8][9][10][11].…”

Section: Introductionmentioning

confidence: 95%

Hypoxia inducible factor (HIF) function in innate immunity and infection

2007

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The hypoxia-inducible transcription factor (HIF-1α) is a major regulator of energy homeostasis and cellular adaptation to low oxygen stress. Recently, HIF-1α has been discovered to function as a global regulator of macrophage and neutrophil inflammatory and innate immune functions, as befits these specialized phagocytic cells who must operate effectively in the hypoxic microenvironments of infected tissues. This review summarizes current knowledge of the role of HIF-1α in mammalian innate immunity, emphasizing insight gained from conditional gene targeting of the transcription factor in the myeloid cell lineage. Dynamic changes in HIF-1α expression in the course of bacterial, viral, or parasitic infections are outlined and inferences drawn regarding the consequences for pathogen and host. A better understanding of HIF-1α function may provide novel and rational approaches for boosting innate immune function in the therapy of certain complicated infectious disease conditions.

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Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!

Cited by 141 publications

References 107 publications

Human Early Fracture Hematoma Is Characterized by Inflammation and Hypoxia

Human Early Fracture Hematoma Is Characterized by Inflammation and Hypoxia

Combined effects of TNF‐α, IL‐1β, and HIF‐1α on MMP‐2 production in ACL fibroblasts under mechanical stretch: An in vitro study

Hypoxia inducible factor (HIF) function in innate immunity and infection

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