The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore

Busillo, John M.; Cidlowski, John A.

doi:10.1016/j.tem.2012.11.005

Cited by 270 publications

(281 citation statements)

References 94 publications

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“…Corneas were harvested and digested in 1.0 to 2.0 mg/mL type 1 collagenase in normal media at 37 C with mechanical dissociation (a pair of corneas/sample). The resulting cell suspension was filtered and labeled for flow cytometric analysis of myeloid and T-cell populations.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…16,22,31 The anti-inflammatory effects of glucocorticoids, such as DEX, are largely considered to be exerted through cross talk with proinflammatory signaling pathways, including NF-kB. 37,38 The analysis of two NF-kBedriven cytokine genes, associated with the immunosuppressive action of DEX, IL-6, and IL-1b, showed a strong trend toward up-regulation at 2 and 8 days pi ( Figure 3A). This increased expression was blocked on DEX treatment ( Figure 3A).…”

Section: The Effect Of Dex On Preserving Corneal Nerves Likely Involvmentioning

confidence: 99%

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IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

Chucair-Elliott

Jinkins

Carr

et al. 2016

The American Journal of Pathology

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Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis characterized by decreased corneal sensation because of damage to the corneal sensory fibers. We and others have reported regression of corneal nerves during acute HSV-1 infection. To determine whether denervation is caused directly by the virus or indirectly by the elicited immune response, mice were infected with HSV-1 and topically treated with dexamethasone (DEX) or control eye drops. Corneal sensitivity was measured using a Cochet-Bonnet esthesiometer and nerve network structure via immunohistochemistry. Corneas were assessed for viral content by plaque assay, leukocyte influx by flow cytometry, and content of chemokines and inflammatory cytokines by suspension array. DEX significantly preserved corneal nerve structure and sensitivity on infection. DEX reduced myeloid and T-cell populations in the cornea and did not affect viral contents at 4 and 8 days post infection. The elevated protein contents of chemokines and inflammatory cytokines on infection were greatly suppressed by DEX. Subconjunctival delivery of neutralizing antibody against IL-6 to infected mice resulted in partial preservation of corneal nerve structure and sensitivity. Our study supports a role for the immune response, but not local virus replication in the development of HSV-1einduced neurotrophic keratitis. IL-6 is one of the factors produced by the elicited inflammatory response to HSV-1 infection contributing to nerve regression.

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Section: Flow Cytometrymentioning

confidence: 99%

Section: The Effect Of Dex On Preserving Corneal Nerves Likely Involvmentioning

confidence: 99%

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

Chucair-Elliott

Jinkins

Carr

et al. 2016

The American Journal of Pathology

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“…3e). For comparative purposes, and given the well-known anti-inflammatory function of GR in keratinocytes (Busillo and Cidlowski, 2013;Sevilla et al, 2013), we also used epidermal GR knock-out cells (GR EKO , Latorre et al, 2013). The B-luciferase activity was four-fold higher in MRdeficient cells relative to CO, and similar to that observed in GR-deficient keratinocytes (Fig.…”

Section: B)mentioning

confidence: 55%

091 Epidermal mineralocorticoid receptor plays beneficial and adverse effects in skin and mediates glucocorticoid responses

Tarín

Sevilla

Sáez

et al. 2016

Journal of Investigative Dermatology

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Glucocorticoids (GCs) regulate skin homeostasis and combat cutaneous inflammatory diseases, however, adverse effects of chronic GC treatments limit their therapeutic use.GCs bind and activate the GC receptor (GR) and the mineralocorticoid receptor (MR), transcription factors that recognize identical hormone responsive elements (HREs).Whether epidermal MR mediates beneficial or deleterious GC effects is of great interest for improving GC-based skin therapies. MR epidermal knock-out (MR EKO ) mice exhibited increased keratinocyte proliferation and differentiation and showed resistance to GC-induced epidermal thinning. However, crucially, loss of epidermal MR rendered mice more sensitive to inflammatory stimuli and skin damage. MR EKO mice showed increased susceptibility to PMA-induced inflammation with higher cytokine induction.Likewise, cultured MR EKO keratinocytes had increased PMA-induced NF-B activation, highlighting an anti-inflammatory function for MR. GC-induced transcription was reduced in MR EKO keratinocytes, at least partially due to decreased recruitment of GR to HRE-containing sequences. Our results support a role for epidermal MR in adult skin homeostasis and demonstrate non-redundant roles for MR and GR in mediating GC actions.3

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“…In fact, an obese mice model induced by high-fat diet had prevented accumulation of adipose tissue macrophages (ATM) after a treatment with dexamethasone, showing the beneficial effects of GC treatment in this context [25] . However, emerging evidences show both proinflammatory and anti-inflammatory actions of GCs, depending on the duration and magnitude of the GC signaling and proinflammatory stimulus [27] . Thus, it is likely that the impact of GCs in cell response is much broader than the interplay between GR and NF-κB or AP-1.…”

Section: Research Highlightmentioning

confidence: 99%

How much we know about the attenuation of insulin signaling in the adipose tissue caused by glucocorticoid treatment?

Rafacho

Nunes²,

Bordin³

2015

Inflamm Cell Signal

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Glucocorticoid (GC) hormone exerts numerous physiological roles that include modulation of immune, nervous, cardiovascular and metabolic systems. Synthetic GCs such as dexamethasone and prednisone/prednisolone are widely prescribed in the clinical context to the treatment of inflammatory-related diseases. In spite of its positive therapeutic effect, GC-based therapies may cause several adverse effects including glucose intolerance and peripheral insulin resistance. Reduction of insulin sensitivity in the adipocytes and adipose tissue caused by GC treatment is associated with increased lipolysis and abnormal Ser phosphorylation of insulin substrate receptor (IRS)-1 and protein kinase B (PKB). However, there is no consensus about the precise mechanisms whereby GC treatment promotes such attenuation in the insulin signaling pathway. In this paper, we will briefly discuss and present some molecular evidences that might be involved with this negative impact of GC in the insulin signaling in the adipose tissue.

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The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore

Cited by 270 publications

References 94 publications

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection

091 Epidermal mineralocorticoid receptor plays beneficial and adverse effects in skin and mediates glucocorticoid responses

How much we know about the attenuation of insulin signaling in the adipose tissue caused by glucocorticoid treatment?

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