Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-α

Mitoma, Hiroki; Horiuchi, Takahiko; Hatta, Nobuaki; Tsukamoto, Hiroshi; Harashima, Shin‐ichi; Kikuchi, Yuji; Otsuka, Junji; Okamura, Seiichi; Fujita, Shigeru; Harada, Mine

doi:10.1053/j.gastro.2004.11.060

Cited by 260 publications

(212 citation statements)

References 49 publications

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“…Infliximab, by virtue of being IgGI antibodies, can activate complement and bind Fc receptor and it also can bind both monomeric and trimeric solTNF and tmTNF, whereas etanercept only binds TNF trimers and interacts with tmTNF with reduced avidity, compared with that of infliximab [82,[110][111][112].…”

Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

117

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Tumor necrosis factor (TNF)-α, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lung. Given that there is significant literature supporting the pathobiologic role of TNF-α in asthma, mainly in severe refractory asthma, and COPD, TNF-α inhibitors (infliximab, golimumab and etanercept) are now regarded as potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-α inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-α inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-α, perhaps in a more carefully selected patient group. TNF-α treatment should therefore not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-α inhibitors.

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Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

117

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“…Subsequent studies suggested that complement-mediated lysis or Ab-dependent cytotoxicity (ADCC) played a role in the effects of these biologics [11]. More recent models postulate that anti-TNF biologics may work by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, or suppression of cytokine production [12]. These in vitro and a few in vivo studies that have given some insight into the possible mechanisms by which anti-TNF agents may improve diseases are described in the following sections and summarized in Tables 1 and 2 and Figs.…”

Section: How Does Tnfα Blockade Work In Disease States?mentioning

confidence: 99%

“…2). The resulting release of intracellular calcium, cytokine production, and E-selectin expression is associated with caspase-dependent apoptosis [12]. This apoptosis does not seem to require Fas-Fas ligand interaction, however [19].…”

Section: Explanation Of Tnf Signalingmentioning

confidence: 99%

“…The three transmembrane serine residue domains on mTNF are essential to its function. It is also likely that p53, a transcription factor that regulates apoptosis and cell cycle arrest, acting through intracellular signaling proteins Bax and Bak, is responsible in part for the INF-induced apoptotic effect [12]. Caspase 8 acts to promote apoptosis through its downstream effects on caspase 3, as well as on proteins that influence mitochondrial permeability, Bcl-2, Bc-xL (anti-apoptotic), Bax and Bak (pro-apoptotic).…”

Section: Explanation Of Tnf Signalingmentioning

confidence: 99%

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TNFα blockade in human diseases: Mechanisms and future directions

Wong

Ziring

Korin

et al. 2008

Clinical Immunology

255

162

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Tumor necrosis factor-alpha (TNFα) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFα antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFα antibodies are effective in other IMIDs. Early efforts at understanding how TNFα antagonists act in IMIDs centered on their ability to neutralize soluble TNFα or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFα blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFα antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFα antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFα antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations.

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“…2. La fixation sur le TNF membranaire peut provoquer un phénomène appelé reverse signaling parce que le signal est déclenché dans la cellule exprimant la cytokine [26,27]. Cela peut induire l'apoptose et l'inhibition de la production de cytokines mais aussi l'activation de cette cellule et la surexpression de sélectines [17,28].…”

Section: Synthèse Revuesunclassified

Protéine de fusion ou anticorps monoclonal

Sibilia

2009

Med Sci (Paris)

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Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-α

Cited by 260 publications

References 49 publications

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

TNFα blockade in human diseases: Mechanisms and future directions

Protéine de fusion ou anticorps monoclonal

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