Differential Local and Systemic Regulation of the Murine Chemokines Kc and Mip2

Call, Douglas R.; Nemzek, Jean A.; Ebong, Samuel; Bolgos, G.; Newcomb, David E.; Wollenberg, Gordon K.; Remick, Daniel G.

doi:10.1097/00024382-200115040-00005

Cited by 79 publications

(53 citation statements)

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“…Our results also indicate that while the in vitro production of KC and MIP-2 are similar, circulating KC levels in vivo are far higher than MIP-2 levels. This observation is identical to the one described for thioglycollate- or glycogen-induced peritonitis (31). While TNF-α is a potent inducer of KC and MIP-2 expression in vivo (32), TNFR deficiency had no effect on PKCα-mediated induction of these 2 chemokines (14).…”

Section: Discussionsupporting

confidence: 71%

CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation

Cataisson

Pearson

Tsien

et al. 2006

Journal of Clinical Investigation

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Transgenic mice overexpressing PKCα in the epidermis (K5-PKCα mice) exhibit an inducible severe intraepidermal neutrophilic inflammation and systemic neutrophilia when PKCα is activated by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This inducible model of cutaneous inflammation was used to define mediators of skin inflammation that may have clinical relevance. Activation of cutaneous PKCα increased the production of the chemotactic factors cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein 2 (MIP-2) in murine plasma. TPA treatment of cultured K5-PKCα keratinocytes also released KC and MIP-2 into culture supernatants through an NF-κB-dependent pathway. MIP-2 and KC mediated the infiltration of neutrophils into the epidermis, since this was prevented by ablating CXCR2 in K5-PKCα mice or administering neutralizing antibodies against KC or MIP-2. The neutrophilia resulted from PKCα-mediated upregulation of cutaneous G-CSF released into the plasma independent of CXCR2. These responses could be inhibited by topical treatment with a PKCα-selective inhibitor. Inhibiting PKCα also reduced the basal and TNF-α-or TPA-induced expression of CXCL8 in cultured psoriatic keratinocytes, suggesting that PKCα activity may contribute to psoriatic inflammation. Thus, skin can be the source of circulating factors that have both local and systemic consequences, and these factors, their receptors, and possibly PKCα could be therapeutic targets for inhibition of cutaneous inflammation.

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Section: Discussionsupporting

confidence: 71%

CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation

Cataisson

Pearson

Tsien

et al. 2006

Journal of Clinical Investigation

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“…Although the affinity of MIP-2 toward CXCR2 is stronger than that of KC (16), there have been few reports suggesting that MIP-2 is a main player in an inflammatory response. In addition, it has been reported that KC and MIP-2 differ, in that KC is a more potent chemoattractant whereas MIP-2 is more active as a regulator of neutrophil degranulation (17,18). In brief, the neutrophil infiltration caused by massive and acute apoptosis appears to be regulated differently from regular inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…Because an IL-8 gene has not been discovered in mouse or rat, these two chemokines are thought to be functional homologues of IL-8 in these rodents (12)(13)(14). Although both MIP-2 and KC bind to CXCR2 (15,16), recent studies showed that KC is a more potent chemoattractant than MIP-2, and that KC seems to be essential for the initiation stage of inflammation (17,18). Consequently, we hypothesized that, when massive and acute apoptosis occurs in vivo, neutrophils infiltrate in response to MIP-2 to play an unknown role possibly unrelated to inflammation.…”

mentioning

confidence: 97%

Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

Iyoda

Nagata

Akashi³

et al. 2005

The Journal of Immunology

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It is generally believed that the clearance of apoptotic cells does not lead to inflammation. In contrast, we previously found that injection of apoptotic cells into the peritoneal cavity induced the expression of an inflammatory chemokine, MIP-2, and infiltration of neutrophils, and that anti-MIP-2 Abs suppressed the infiltration significantly. Because our previous study showed that whole-body x-irradiation caused neutrophil infiltration into the thymus along with T cell apoptosis, we examined the role of neutrophils in apoptotic cell clearance. Neutrophil infiltration reached a peak 12 h after irradiation with 1 Gy of x-rays. Immunohistological analysis revealed that apoptotic cells disappeared dramatically from 10.5 to 12 h after x-irradiation. As neutrophils moved from an inner area of the cortex to the periphery, apoptotic cells disappeared concomitantly. Either anti-MIP-2 or anti-CXCR2 Abs suppressed neutrophil infiltration significantly, and the suppression of neutrophil infiltration by anti-MIP-2 Abs delayed the disappearance of apoptotic cells. Moreover, macrophage-mediated digestion of apoptotic thymocytes was accelerated in vitro on coculturing with neutrophils, even if neutrophils were separated from macrophages. These results suggest that neutrophils are recruited to the thymus mainly by MIP-2 after whole-body x-irradiation and that such neutrophils may not induce inflammation but rather accelerate complete digestion of apoptotic cells by macrophages.

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“…55 MIP-2, also known as CXCL2, and KC were reported as being important chemoattractant factors to draw neutrophils to the site of inflammation. [56][57][58] Regarding the effects of α-bis on the production of proinflammatory cytokines, the free form was able to reduce the MIP-2 level only at the highest tested dose. However, in line with the results so far described, the α-bis-LNCs formulation lowered the levels of all measured cytokines at the three tested doses.…”

mentioning

confidence: 97%

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

D'Almeida¹,

Oliveira²,

Souza³

et al. 2017

IJN

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Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg −1 ) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, free α-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS.

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Differential Local and Systemic Regulation of the Murine Chemokines Kc and Mip2

Cited by 79 publications

References 0 publications

CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation

CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation

Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

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Differential Local and Systemic Regulation of the Murine Chemokines Kc and Mip2

Cited by 79 publications

References 0 publications

CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation

CXCR2 ligands and G-CSF mediate PKC -induced intraepidermal inflammation

Neutrophils Accelerate Macrophage-Mediated Digestion of Apoptotic Cells In Vivo as Well as In Vitro

&alpha;-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice

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α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice