Low‐molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor‐<i>κ</i>B in LPS‐stimulated human monocytes

Hochart, Hélène; Jenkins, P. Vincent; Smith, Owen; White, Barry

doi:10.1111/j.1365-2141.2006.05959.x

Cited by 109 publications

(95 citation statements)

References 30 publications

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“…Heparin and its derivatives have been shown to possess anti-inflammatory properties in various cell and animal models (Carr, 1979;Young, 2008). These agents inhibit NF-kB activation and secretion of inflammatory cytokines such as IL-8, TNFa, and IL-6 from endotoxin-stimulated monocytes (Hochart et al, 2006). Similarly, heparin and ODSH have been reported to protect against neutrophilic elastase-mediated lung injury (Fryer et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Partially-desulfated heparin improves survival inPseudomonaspneumonia by enhancing bacterial clearance and ameliorating lung injury

Sharma

Patel

et al. 2013

Journal of Immunotoxicology

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Nosocomial pneumonia (NP, or hospital-acquired pneumonia) is associated with infections originating from hospital-borne pathogens. Persistent microbial presence and acute lung injury are common features of these infections, contributing to the high mortality rates and excessive financial burden for these patients. Pseudomonas aeruginosa (PA), a gram-negative opportunistic pathogen, is one of the prominent pathogens associated with NP. PA pneumonia is characterized by excessive secretion of inflammatory cytokines, neutrophil infiltration, and subsequent lung damage. The persistent presence of PA along with overwhelming inflammatory response is suggestive of impairment in innate immunity. High mobility group box 1 (HMGB1), a recently discovered potent pro-inflammatory cytokine, plays an important role in PA lung infections by compromising innate immunity via impairing phagocyte function through toll-like receptors (TLR) TLR2 and TLR4. ODSH (2-O, 3-O-desulfated heparin), a heparin derivative with significant anti-inflammatory properties but minimal anti-coagulatory effects, has been shown to reduce neutrophilic lung injury in the absence of active microbial infections. This study examined the effects of ODSH on PA pneumonia. This study demonstrates that ODSH not only reduced PA-induced lung injury, but also significantly increased bacterial clearance. The ameliorated lung injury, together with the increased bacterial clearance, resulted in marked improvement in the survival of these animals. The resulting attenuation in lung injury and improvement in bacterial clearance were associated with decreased levels of airway HMGB1. Furthermore, binding of HMGB1 to its receptors TLR2 and TLR4 was blunted in the presence of ODSH. These data suggest that ODSH provides a potential novel approach in the adjunctive treatment of PA pneumonia.

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Section: Discussionmentioning

confidence: 99%

Partially-desulfated heparin improves survival inPseudomonaspneumonia by enhancing bacterial clearance and ameliorating lung injury

Sharma

Patel

et al. 2013

Journal of Immunotoxicology

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“…Like HP, LH is known to suppress LPS-induced inflammation in vitro 24) and in vivo. 25) In addition, LH is much more likely to bind to vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).…”

Section: Resultsmentioning

confidence: 99%

Anti-inflammatory Effect of Self-assembling Glycol-Split Glycosaminoglycan-Stearylamine Conjugates in Lipopolysaccharide-Stimulated Macrophages

Yanamoto

Babazada

Sakai

et al. 2017

Biological & Pharmaceutical Bulletin

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Glycosaminoglycans (GAGs) play important roles in various biological processes such as cell adhesion and signal transduction, as well as promote anti-inflammatory activity. We previously revealed that glycolsplit heparin (HP)-aliphatic amine conjugates form self-assembled nanoparticles and suppress the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated macrophages much more strongly than native HP (J. Control. Release, 194, 2014, Babazada et al.). Considering that HP is not the only GAG to have anti-inflammatory activity, the present study was initiated to examine whether conjugation of GAGs with aliphatic amines is generally effective in their activity augmentation against LPS-stimulated macrophages. We newly synthesized the stearylamine conjugates of chondroitin sulfate (CS), hyaluronic acid (HA), and low-molecular-weight heparin (LH), and investigated the effect of the position and degree of sulfation and molecular weight of GAGs on their anti-inflammatory activity. All of the conjugates formed self-assembled nanoparticles in aqueous solution. The IC 50 value for suppression of TNF-α production from the macrophages was the smallest with the derivative of LH, followed by HP, CS, and HA. The degree of sulfation appeared to be important in determining their anti-inflammatory activity, which would correspond to previous results using the derivatives of siteselectively desulfated HP. Comparison of HP and LH derivatives revealed that fractionated smaller heparin has greater anti-inflammatory activity.Key words glycosaminoglycan; self-assembled nanoparticle; anti-inflammatory activity; Toll-like receptor 4; macrophage; structure-activity relationship Glycosaminoglycans (GAGs) are linear polysaccharides that play important roles in processes such as cell adhesion and signal transduction. 1) Heparin (HP) is one of the highly sulfated GAGs that consist of repeats of alternating uronic acid and D-glucosamine.2) HP is a well-known anticoagulant that activates antithrombin, leading to anticoagulation 3) ; moreover, it has a variety of additional biological effects such as antiangiogenesis and anti-inflammation. Chondroitin sulfate (CS), consisting of repeats of alternating D-glucuronic acid and N-acetyl-D-galactosamine, 2,4) is used clinically to reduce pain and improve articular function in patients with osteoporosis.5,6) Hyaluronic acid (HA) consists of repeats of alternating D-glucuronic acid and N-acetyl-D-glucosamine, but characteristically lacks sulfo groups. 2,4) HA has been used to protect synovial membranes and heal injuries. [7][8][9] Although the biological activity varies for each GAG, a common feature is the presence of an anti-inflammatory effect. Several in vitro [10][11][12][13][14] and in vivo 15,16) studies have shown that HP, CS, and HA suppress the lipopolysaccharide (LPS)-induced production of inflammatory cytokines by inhibiting the activation of MyD88, p38 mitogen-activated protein kinase (MAPK), an...

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“…6 The low-molecular-weight heparin reduces translocation of tumor necrosis factor alfa (TNF-a), interleukin (IL)-8, IL-6, IL-1B and nuclear factor (NF) kappa B (kB) which are caused by lipopolysaccharides distinctly. 7 Enoxaparin is low-molecular-weight heparin. Epidemically it is used at treatment of thromboembolic diseases as similar like other lowmolecular-weight heparin; it has the better pharmaco-dynamic parametres (properties) and more reliable than heparin.…”

Section: 3mentioning

confidence: 99%

The effectiveness of treatment with enoxaparin in lichen planus

Uçmak

Balci²,

Harman³

2012

J Clin Exp Invest

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ÖZETAmaç: Heparin analoglarının düşük dozlarının antiproliferatif ve immünmodülatör etkilerinin olduğu bilinmektedir. Bu çalışmanın amacı; liken planusta düşük doz enoxaparinin etkinliğini değerlendirmektir. Gereç ve yöntem:Liken planus tanısı alan 21 hasta 12 hafta boyunca tedavi edildi. Hastalara her hafta 3 mg enoxaparin subkutan enjeksiyonla yapıldı. Etki ve güven-lik verileri kaydedildi. Bulgular:Tam iyileşme hastaların 15' inde (%71), belirgin düzelme 4' ünde (%19) tespit edildi. Hastaların 2'sinde (%9) tedaviye yanıt alınmadı. Tedavi sonucunda en iyi yanıt, liken planusun akut generalize tipinde görüldü.Sonuç: Sonuç olarak enoxaparin tedavisinin liken planusta etkili bir tedavi seçeneği olabileceği kanaatine varıldı.Anahtar kelimeler: Liken planus, enoxaparin, tedavi ABSTRACT Objectives: As it is known, the low doses of Heparin's analogues have the antiproliferative and immunomodulator activities. This research aims to evaluate the activity of enoxaparin by using the low doses. Materials and methods:21 patients with lichen planus diagnosis have been cured within 12 weeks. 3 mg of enoxaparin has been used for subcutaneus injection to all of patients weekly. The efficient and reliable data has been saved. Results:The perfect recovery has been observed 15 (71%) of 21 patients, the distinct recovery has been observed 4 (19%) of 21 patients. The treatment has not given response on 2 (9%) of 21 patients. The best score has been received on acute generalized type of Lichen Planus. Conclusions:As the result; it has been reported that enoxaparin treatment can be an effective choice in Lichen Planus medication. J Clin Exp Invest 2011; 3(2): 172-173

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Low‐molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor‐κB in LPS‐stimulated human monocytes

Cited by 109 publications

References 30 publications

Partially-desulfated heparin improves survival inPseudomonaspneumonia by enhancing bacterial clearance and ameliorating lung injury

Partially-desulfated heparin improves survival inPseudomonaspneumonia by enhancing bacterial clearance and ameliorating lung injury

Anti-inflammatory Effect of Self-assembling Glycol-Split Glycosaminoglycan-Stearylamine Conjugates in Lipopolysaccharide-Stimulated Macrophages

The effectiveness of treatment with enoxaparin in lichen planus

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