Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS-induced inflammation in mouse chondrocytes

Campo, Giuseppe M.; Avenoso, Angela; Campo, Salvatore; D’Ascola, Angela; Nastasi, Giancarlo; Calatroni, Alberto

doi:10.1016/j.biochi.2009.10.006

Cited by 149 publications

(137 citation statements)

References 42 publications

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“…The data of the present study concur with results previously obtained [15][16] and allow us to hypothesize the following integrated mechanism (Scheme 1). In normal conditions, native HA is produced on the inner surface of the plasma membrane and extruded into the extracellular environment.…”

Section: Hypothetical Mechanism From the Reformulation Of The Resultssupporting

confidence: 92%

“…Recent data have demonstrated the involvement of low molecular weight HA and other GAGs in the modulation of inflammation by interacting with TLR-4 in mouse cartilage chondrocytes [16,25]. Articular cartilage homeostasis is in fact a result of an intricate interplay between anabolic and catabolic, antiand pro-inflammatory, anti-and pro-apoptotic mediators [26], and chondrocytes are the versatile regulators of cartilage equilibrium.…”

Section: Discussionmentioning

confidence: 99%

“…As, in two separated experiments, we previously reported that low molecular weight HA (50 kD) significantly activated NF-kB-induced transcription of pro-inflammatory mediators [15][16] by stimulating TLR-4 or CD44 receptors, the aim of the present study was to evaluate whether the inflammation stimulated by low molecular weight HA or other small HA fragments could be the result of the activation of both TLR-4 and CD44 receptors. For this purpose we treated normal human chondrocytes with a specific HA oligosaccharide containing only six monosaccharides (6mer) since previous reports [17][18] had shown that HA at this size was able to stimulate inflammation by interacting with both receptors TLR-4 and CD44.…”

Section: Page 4 Of 30mentioning

confidence: 95%

“…It has also been reported that fragments of HA or HA at low molecular weight are able to interact with TLR-4 and CD44 receptors, thereby stimulating inflammation or increasing the inflammatory mechanism previously induced by other agents in different cell types [11][12][13][14][15][16]. Hence, the generation of lower molecular weight HA in pathologies may act as an endogenous danger signal, leading to the activation of both innate and acquired immunity.…”

Section: Page 4 Of 30mentioning

confidence: 99%

“…After centrifugation at 8,000 x g, the supernatant containing the cytosolic fraction was stored at -80 °C, while the pellet containing the nuclear portion was then re-suspended in the apposite extraction buffer and the nuclei were disrupted by a series of drawing and ejecting actions. The nuclei suspension was then centrifuged at 16,000 x g. The supernatant fraction was the nuclear extract. After determining protein concentration and adjustment to a final concentration of approximately 4.0 mg/ml, this extract was stored in aliquots at -80° C for the subsequent NF-kB assay.…”

Section: Page 8 Of 30mentioning

confidence: 99%

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Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes

Campo

Avenoso

Campo

et al. 2010

Biochemical Pharmacology

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and cd44 receptors in human chondrocytesGiuseppe M. Campo, Angela Avenoso, Salvatore Campo, Angela D'Ascola, Giancarlo Nastasi, Alberto CalatroniTo cite this version: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 Adding HA fragments to chondrocyte cultures up-regulated CD44 and TLR-4 expression, activated NF-kB translocation and increased the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β.The addition of a specific CD44 blocking antibody reduced CD44 and all inflammatory cytokine expression as well as protein production. However, cytokine expression remained significantly higher than in untreated chondrocytes. TLR-4 expression was not affected. The treatment with TLR-4 blocking antibody decreased TLR-4 and inflammatory cytokine expression, although cytokine expression was significantly higher than in control cells. CD44 expression was unaffected.The addition of both CD44 and TLR-4 blocking antibodies significantly reduced CD44, TLR-4 and inflammatory cytokine expression.

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Section: Hypothetical Mechanism From the Reformulation Of The Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Page 4 Of 30mentioning

confidence: 95%

Section: Page 4 Of 30mentioning

confidence: 99%

Section: Page 8 Of 30mentioning

confidence: 99%

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Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes

Campo

Avenoso

Campo

et al. 2010

Biochemical Pharmacology

Self Cite

138

102

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Biopolysaccharides: Properties and Applications

Tunçer

2021

Polysaccharides

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Hyaluronan Metabolism in Urologic Cancers

Donelan,

Brisbane,

O'Malley

et al. 2023

Advanced Biology

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Hyaluronan (HA) is one of the major components of the extracellular matrix in tumor tissue. Recent reports have made it clear that the balance of HA synthesis and degradation is critical for tumor progression. HA is synthesized on the cytoplasmic surface of the plasma membrane by hyaluronan synthases (HAS) and extruded into the extracellular space. Excessive HA production in cancer is associated with enhanced HA degradation in the tumor microenvironment, leading to the accumulation of HA fragments with small molecular weight. These perturbations in both HA synthesis and degradation may play important roles in tumor progression. Recently, it has become increasingly clear that small HA fragments can induce a variety of biological events, such as angiogenesis, cancer‐promoting inflammation, and tumor‐associated immune suppression. Progression of urologic malignancies, particularly of prostate and bladder cancers, as well as of certain types of kidney cancer show markedly perturbed metabolism of tumor‐associated HA. This review highlights the recent research findings regarding HA metabolism in tumor microenvironments with a special focus on urologic cancers. It also will discuss the potential implications of these findings for the development of novel therapeutic interventions for the treatment of prostate, bladder, and kidney cancers.

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Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS-induced inflammation in mouse chondrocytes

Cited by 149 publications

References 42 publications

Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes

Small hyaluronan oligosaccharides induce inflammation by engaging both toll-like-4 and CD44 receptors in human chondrocytes

Biopolysaccharides: Properties and Applications

Hyaluronan Metabolism in Urologic Cancers

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