Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation

Ruppert, Shannon M.; Hawn, Thomas R.; Arrigoni, Alberto; Wight, Thomas N.; Bollyky, Paul L.

doi:10.1007/s12026-014-8495-2

Cited by 150 publications

(157 citation statements)

References 77 publications

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“…TLRs 2 and 4 and CD44 each represent cell surface receptors of HA32 and the potential roles of these receptors in enhancing the innate response of the vaginal cells to flagellin, in the presence of HA, was explored using a gene knockdown approach (Supplementary figure 3). The effects of silencing the TLR5 gene encoding TLR5, which mediates the host response to flagellin, were also examined.…”

Section: Resultsmentioning

confidence: 99%

“…LMW HA has been reported to function through TLRs 2 and 4, but independently of CD44, to stimulate the synthesis of host defence effectors including BD2 and SLPI in vaginal cells 31. Surprisingly, however, in view of its pro‐inflammatory properties,32 these responses observed using the VK2E6/E7 cell model were reported to be independent of pro‐inflammatory cytokine production.…”

Section: Discussionmentioning

confidence: 97%

“…High molecular weight hyaluronic acid has been shown to protect against inflammation, and the mechanism is suggested to involve cross‐linking of the glycosaminoglycan with transmembrane CD44 receptors 32. The importance of the cell adhesion receptor molecule CD44 in this process has been further demonstrated in vivo using CD44 −/− mice, with the accumulation of LMW HA associated with and responsible for an exaggerated inflammatory response 46, 47.…”

Section: Discussionmentioning

confidence: 99%

“…The glycosaminoglycan HA is found naturally throughout the body as a major constituent of the extracellular matrix,34 and functions in healthy tissues to regulate cell growth, differentiation and to inhibit inflammation 32. Clinically, bladder instillations containing HA have been shown to reduce UTI episodes and pain30, 35, 36 with in vivo studies suggesting that HA treatment is associated with reduced bacterial growth 37.…”

Section: Discussionmentioning

confidence: 99%

“…While the mechanisms underpinning signal amplification remain obscure, cooperation between receptors either physically or through shared intracellular signalling molecules cannot be excluded. The potential roles of other HA binding molecules such as the hyaladherins, RHAMM, LYVE‐1 and HARE32 also remain to be explored.…”

Section: Discussionmentioning

confidence: 99%

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High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

et al. 2018

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ObjectivesRecurrent urinary tract infections are associated with uropathogenic Escherichia coli (UPEC) ascending and infecting the urinary tract. Antibiotics provide only symptomatic relief, not prevent recurrence. Clinical evidence suggests that intravesical glycosaminoglycan therapy, such as hyaluronic acid (HA), helps reduce UTI recurrence. This has been investigated here using in vitro systems modelling the urogenital tract tissues.Methods RT4 bladder cells were preconditioned with high molecular weight HA (> 1500 kDa) at 2 mg mL−1 and challenged with UPEC to analyse barrier protection and bacterial adherence. Untreated and HA‐preconditioned VK2 E6/E7 vaginal cells were challenged with E. coli flagellin (50 ng mL−1) to mimic bacterial challenge, and media analysed for lipocalin‐2, human β‐defensin 2 and interleukin‐8 by ELISA. Experiments were repeated after siRNA knockdown of Toll‐like receptors 2, 4 and 5, and CD44 to investigate signalling.ResultsMicroscopic analyses showed reduced bacterial adherence and urothelial disruption with HA, suggesting that HA functions as a barrier protecting the epithelium from bacterial infection. Cells treated with HA and flagellin simultaneously produced more of the host antimicrobial peptide LCN2 and pro‐inflammatory IL‐8 (P < 0.05) compared to the no HA/flagellin challenges. Increased gene expression of DEFB4 (P < 0.05), but not the hBD2 peptide, was observed in the HA/flagellin‐challenged cells.ConclusionThese data suggest that exogenous HA has potential to protect the urogenital epithelia from UPEC infection via a two‐pronged approach that involves the physical enhancement of the epithelial barrier and augmentation of its innate immune response.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

et al. 2018

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Recent Advances in Antiinflammatory Material Design

Lebaudy

Fournel

Lavalle

et al. 2020

Adv Healthcare Materials

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Implants and prostheses are widely used to replace damaged tissues or to treat various diseases. However, besides the risk of bacterial or fungal infection, an inflammatory response usually occurs. Here, recent progress in the field of anti‐inflammatory biomaterials is described. Different materials and approaches are used to decrease the inflammatory response, including hydrogels, nanoparticles, implant surface coating by polymers, and a variety of systems for anti‐inflammatory drug delivery. Complex multifunctional systems dealing with inflammation, microbial infection, bone regeneration, or angiogenesis are also described. New promising stimuli‐responsive systems, such as pH‐ and temperature‐responsive materials, are also being developed that would enable an “intelligent” antiinflammatory response when the inflammation occurs. Together, different approaches hold promise for creation of novel multifunctional smart materials allowing better implant integration and tissue regeneration.

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Multifunctional Hydrogels for the Healing of Diabetic Wounds

Xiang,

Guo,

Jia

et al. 2023

Adv Healthcare Materials

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The healing of diabetic wounds is hindered by various factors, including bacterial infection, macrophage dysfunction, excess proinflammatory cytokines, high levels of reactive oxygen species, and sustained hypoxia. These factors collectively impede cellular behaviors and the healing process. Consequently, this review presents intelligent hydrogels equipped with multifunctional capacities, which enable them to dynamically respond to the microenvironment and accelerate wound healing in various ways, including stimuli ‐responsiveness, injectable self‐healing, shape ‐memory, and conductive and real‐time monitoring properties. The relationship between the multiple functions and wound healing is also discussed. Based on the microenvironment of diabetic wounds, antibacterial, anti‐inflammatory, immunomodulatory, antioxidant, and pro‐angiogenic strategies are combined with multifunctional hydrogels. The application of multifunctional hydrogels in the repair of diabetic wounds is systematically discussed, aiming to provide guidelines for fabricating hydrogels for diabetic wound healing and exploring the role of intelligent hydrogels in the therapeutic processes.

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Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation

Cited by 150 publications

References 77 publications

High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

High molecular weight hyaluronic acid: a two‐pronged protectant against infection of the urogenital tract?

Recent Advances in Antiinflammatory Material Design

Multifunctional Hydrogels for the Healing of Diabetic Wounds

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