Role of lipocortin‐1 in the anti‐hyperalgesic actions of dexamethasone

  title={Role of lipocortin‐1 in the anti‐hyperalgesic actions of dexamethasone},
  author={S{\'e}rgio H. Ferreira and Fernando de Q Cunha and Berenice B. Lorenzetti and M{\'a}rcia Antoniazi Michelin and Mauro Perretti and Roderick John Flower and Stephen Poole},
  journal={British Journal of Pharmacology},
The effect of dexamethasone, lipocorton‐12–26 and an antiserum to lipocortin‐12–26 (LCPS1) upon the hyperalgesic activities in rats of carrageenin, bradykinin, tumour necrosis factor α (TNFα), interleukin‐12, interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), prostaglandin Eβ (PGE2) and dopamine were investigated in a model of mechanical hyperalgesia. Hyperalgesic responses to intraplantar ( injections of carrageenin (100 μg), bradykinin (500 ng), TNFα (2.5 pg), IL‐1β (0.5 pg), and IL‐6 (1.0 ng… 
Down‐regulation of microglial cyclo‐oxygenase‐2 and inducible nitric oxide synthase expression by lipocortin 1
The hypothesis that lipocortin 1 may foster neuroprotection by limiting microglial activation, through autocrine and paracrine mechanisms is supported.
Differential modulatory effects of Annexin 1 on nitric oxide synthase induction by lipopolysaccharide in macrophages
Differential effects on iNOS expression in macrophages are seen when comparing acute administration of ANXA1 peptides versus the chronic endogenous over‐expression of AN XA1, suggesting that ANxA1 may modify iN OS levels by post‐transcriptional mechanisms.
Annexin 1: A glucocorticoid‐inducible protein that modulates inflammatory pain
In general, ANXA1 is a potential mediator for anti‐nociception and the role with its receptor constitute attractive targets for developing anesthesia and analgesic drugs, and their interaction may prove to be a useful strategy to treat inflammatory pain.
A cascade of cytokines mediates mechanical inflammatory hypernociception in mice.
Results extend to mice the concept that the release of primary mediators responsible for hypernociception is preceded by a cascade of cytokines.
The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines
The results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.
Inhibiting the Cannabinoid Catabolic Enzyme MAGL to Potentiate the Anti-Arthritic Properties of the Synthetic Glucocorticoid Dexamethasone
It is found that, although both JZL184 and DEX significantly attenuated proinflammatory cytokine levels in the paws of CIA mice, only DEX decreased pain-related behaviors and paw swelling, and combined administration of a sub-effective dose both drugs was ineffective overall.
Aberrant inflammation and resistance to glucocorticoids in Annexin 1−/− Mouse
  • R. Hannon, J. Croxtall, R. Flower
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
It is reported that mice lacking the Anx‐1 gene exhibit a complex phenotype that includes an altered expression of other annexins as well as of COX‐2 and cPLA2 in response to carrageenin‐ or zymosan‐induced inflammation.


Bradykinin initiates cytokine‐mediated inflammatory hyperalgesia
Data show that bradykinin can initiate the cascade of cytokine release that mediates hyperalgesic responses to carrageenin and endotoxin, and suggests that the release of hyperAlgesic cytokines can be initiated independently of bradyKinin BK2 receptors.
The pivotal role of tumour necrosis factor α in the development of inflammatory hyperalgesia
Results show that TNFα has an early and crucial role in the development of inflammatory hyperaglesia and the finding that the production of these cytokines is inhibited by steroidal anti‐inflammatory drugs provides a mechanism of action for these drugs in the treatment ofinflammatory hyperalgesia.
The role of lipocortin‐1 in dexamethasone‐induced suppression of PGE2 and TNFα release from human peripheral blood mononuclear cells
The results of the present study implicate endogenousLC‐1 in glucocorticoid suppression of TNFα and PGE2 release from human PBMC and suggest an extracellular site of action for LC‐1.
Acute inflammatory response in the mouse: exacerbation by immunoneutralization of lipocortin 1
An immuno‐neutralization strategy was employed to investigate the role of endogenous lipocortin 1 in acute inflammation in the mouse and the recruitment of PMN into the zymosan inflamed air‐pouches by 24 h had declined substantially.
Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia
It is demonstrated that IL‐1β contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.
The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia.
The delineation of the role of TNF alpha,IL-1 beta, IL-6 and IL-8 in the development of inflammatory hyperalgesia taken together with the finding that the production of these cytokines is inhibited by steroidal anti-inflammatory drugs provides a mechanism of action for these drugs in the treatment ofinflammatory hyperalGESia.
Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor α
The elevation of TNFα in inflammation, by virtue of its capacity to induce IL‐1β and NGF, may contribute to the initiation of inflammatory hyperalgesia.
Cytokine inhibition by a novel steroid, mometasone furoate.
The inhibition of the production of proinflammatory mediators by extremely low concentrations of mometasone furoate suggests that this steroid should be highly effective in various disorders.
Lipocortin-1: cellular mechanisms and clinical relevance.
Lipocortin-1 fragments inhibit neutrophil accumulation and neutrophil-dependent edema in the mouse. A qualitative comparison with an anti-CD11b monoclonal antibody.
This study confirms the activity of LC1 in another model of experimental inflammation and suggests that it acts partly through inhibition of leukocyte activation with an overall effect qualitatively comparable to the blocking of CD11b portion of a beta 2-integrin complex.