Hyaluronan, a Crucial Regulator of Inflammation

Petrey, Aaron C.; Motte, Carol A. de la

doi:10.3389/fimmu.2014.00101

Cited by 382 publications

(357 citation statements)

References 201 publications

(210 reference statements)

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“…IL-1␤ treatment caused no visible change in the distribution of CD44 in keratinocytes. This is unlike the clustering or capping seen in lymphocytes and macrophages during their differentiation and activation (25). At the submicroscopic level, however, dimerization or oligomerization of CD44 was revealed in the IL-1␤-treated cultures.…”

Section: Regulation Of Cd44 Expression and Phosphorylation By Il-1␤-imentioning

confidence: 61%

Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats

Jokela¹,

Oikari²,

Takabe

et al. 2015

Journal of Biological Chemistry

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Background: Interleukin-1␤ recruits leukocytes at the site of inflammation. Results: The interleukin-1␤-induced hyaluronan coat increased monocyte binding to keratinocytes through ezrin-associated CD44 homomers, enabled by reduced serine 325 phosphorylation. Conclusion:The organization of the cell surface hyaluronan coat is controlled by phosphorylation of CD44. Significance: Interleukin-1␤ release in inflamed tissues triggers signals that increase hyaluronan-dependent leukocyte binding.

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Section: Regulation Of Cd44 Expression and Phosphorylation By Il-1␤-imentioning

confidence: 61%

Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats

Jokela¹,

Oikari²,

Takabe

et al. 2015

Journal of Biological Chemistry

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“…Bacterial infection and cell injury are associated with hyaluronidase activity48 and the accumulation of LMW material. Moreover, the inappropriate clearance and persistence of LMW HA links to multiple inflammatory pathologies including arthritis, lung fibrosis49 and potentially interstitial cystitis 50. While the lack of innate responses to the HMW material alone suggested no contamination with LMW material, it cannot be excluded the endogenous production of LMW HA during the challenge period was responsible for the enhanced effector responses.…”

Section: Discussionmentioning

confidence: 99%

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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“…Therefore, these results might be of relevance in clinical practice to optimize the conditions for promoting and preserving the quality of oocytes during handling and culture of COCs retrieved from patients enrolled in programs of assisted reproduction. In addition, it will be of interest to determine whether the dual action of cAMP in the cumulus is exerted also on other HA-rich tissues, particularly at the inflammation site, where hyaluronan is expressed (92) and the protective effect of cAMP elevation through phosphodiesterase inhibitors has been proven (93)(94)(95).…”

Section: Discussionmentioning

confidence: 99%

Cyclic AMP-elevating Agents Promote Cumulus Cell Survival and Hyaluronan Matrix Stability, Thereby Prolonging the Time of Mouse Oocyte Fertilizability

Giacomo

Camaioni

Klinger

et al. 2016

Journal of Biological Chemistry

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Cumulus cells sustain the development and fertilization of the mammalian oocyte. These cells are retained around the oocyte by a hyaluronan-rich extracellular matrix synthesized before ovulation, a process called cumulus cell-oocyte complex (COC) expansion. Hyaluronan release and dispersion of the cumulus cells progressively occur after ovulation, paralleling the decline of oocyte fertilization. We show here that, in mice, postovulatory changes of matrix are temporally correlated to cumulus cell death. Cumulus cell apoptosis and matrix disassembly also occurred in ovulated COCs cultured in vitro. COCs expanded in vitro with FSH or EGF underwent the same changes, whereas those expanded with 8-bromo-adenosine-3,5-cyclic monophosphate (8-Br-cAMP) maintained integrity for a longer time. It is noteworthy that 8-Br-cAMP treatment was also effective on ovulated COCs cultured in vitro, prolonging the vitality of the cumulus cells and the stability of the matrix from a few hours to >2 days. Stimulation of endogenous adenylate cyclase with forskolin or inhibition of phosphodiesterase with rolipram produced similar effects. The treatment with selective cAMP analogues suggests that the effects of cAMP elevation are exerted through an EPAC-independent, PKA type II-dependent signaling pathway, probably acting at the post-transcriptional level. Finally, overnight culture of ovulated COCs with 8-Br-cAMP significantly counteracted the decrease of fertilization rate, doubling the number of fertilized oocytes compared with control conditions. In conclusion, these studies suggest that cAMP-elevating agents prevent cumulus cell senescence and allow them to continue to exert beneficial effects on oocyte and sperm, thereby extending in vitro the time frame of oocyte fertilizability.

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Hyaluronan, a Crucial Regulator of Inflammation

Cited by 382 publications

References 201 publications

Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats

Interleukin-1β-induced Reduction of CD44 Ser-325 Phosphorylation in Human Epidermal Keratinocytes Promotes CD44 Homomeric Complexes, Binding to Ezrin, and Extended, Monocyte-adhesive Hyaluronan Coats

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

Cyclic AMP-elevating Agents Promote Cumulus Cell Survival and Hyaluronan Matrix Stability, Thereby Prolonging the Time of Mouse Oocyte Fertilizability

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