Glucocorticoid dexamethasone down-regulates basal and vitamin D3 induced cathelicidin expression in human monocytes and bronchial epithelial cell line

Kulkarni, Nikhil Nitin; Gunnarsson, Hörður Ingi; Yi, Zhaoxiang; Guðmundsdóttir, Steinunn; Sigurjónsson, Ólafur E.; Agerberth, Birgitta; Guðmundsson, Guðmundur H.

doi:10.1016/j.imbio.2015.09.001

Cited by 22 publications

(21 citation statements)

References 23 publications

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“…CAMP exerts its anti-microbial activity through various mechanisms including the disruption of the bacterial cell wall, neutralization of lipopolysaccharide, and promotion of neutrophil chemotaxis (Burton and Steel 2009;Larrick et al 1995;Nijnik et al 2012). The CAMP gene is reported to be up-regulated by 1,25D3 in both human monocytes/macrophages and keratinocytes, suggesting that CAMP represents a vitamin-D-regulated gene in these human cell types (Liu et al 2006(Liu et al , 2007White 2010;Kulkarni et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α

et al. 2016

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The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti-microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity. Nuclear VDR immunoreactivity was demonstrated in human skin keratinocytes (HaCaT cells). Gene analysis revealed that human skin biopsies expressed higher levels of both CAMP and RXRα mRNA than human gingival biopsies, whereas VDR and RXRβ transcript levels were similar in skin and gingiva. In HaCaT cells, treatment with 1,25D3 (5 nM and 1 μM) for 4 and 24 h up-regulated CAMP mRNA several fold, and treatment with 1,25D3 for 24 h increased protein expression of the pro-form of LL-37 (hCAP-18) by about 13 times. The 1,25D3-evoked stimulation of HaCaT CAMP expression was associated with attenuated VDR mRNA and protein expression. Treatment with RXRα short interfering RNA reversed the 1,25D3-induced CAMP expression in HaCaT cells, showing that RXRα is involved in the up-regulation of CAMP by 1,25D3. We conclude that the 1,25D3-evoked stimulation of CAMP expression in human skin keratinocytes is dependent on RXRα but is not associated with the up-regulation of VDR expression.

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Section: Introductionmentioning

confidence: 99%

Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α

et al. 2016

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“…Vitamin D3 initiates its antibiotic function through the stimulation of antimicrobial peptides, including cathelicidin antimicriobial peptide (CAMP) (15,16). Cathelicidin is primarily produced by phagocytes and epithelial cells, and exerts biological functions by mediating defense against microbial invasion.…”

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confidence: 99%

25-Hydroxyvitamin D<sub>3</sub> Alleviates Experimental Periodontitis via Promoting Expression of Cathelicidin in Mice with Type 2 Diabetic Mellitus

Xinyi

Zhang

Wang

et al. 2018

J Nutr Sci Vitaminol

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Type 2 diabetic mellitus is manifested by metabolic impairments with high prevalence worldwide, of which periodontitis represents a typical oral complication (also called diabetic periodontitis). Oral epithelia bear the brunt of periodontal damage from microscopic intruders; thus the defense function of epithelial cells is of vital significance. We have previously proved that 25-hydroxyvitamin D3 (25-OHD3) altered the expression of cathelicidin antimicrobial peptide in oral epithelial cells in vitro. Herein, we discovered that 25-OHD3 intraperitoneal injection attenuated periodontal inflammation by promoting cathelicidin production in gingival epithelia and reducing fasting glucose of diabetic mice. Dotblotting of serum showed cathelicidin secretion was consistent with 25-OHD3 treatment. Immunochemistry exhibited enhanced expression of cathelicidin and vitamin D receptors along with reduced expression of TLR4 in diabetic mice. Stereomicroscope showed less alveolar bone loss when injected with 25-OHD3.These results showed 25-OHD3 can promote cathelicidin and ameliorate the severity of diabetic periodontitis. Our study complemented the mechanism of cathelicidin and extended knowledge of 25-OHD3's role in diabetic periodontitis.

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“…Therefore, a possible explanation for the decreased MRSA colonization in dexamethasone-treated animals is the stimulation of innate immunity by low-dose dexamethasone resulting in more rapid MRSA elimination. According to Kulkarni et al, dexamethasone treatment decreases the gene expression of antimicrobial peptides (AMPs)-secreted by innate immune cells (monocytes, macrophages, neutrophils and epithelial cells)-in THP-1 monocytes [21]. AMPs are involved in the early defense against pathogens and play, inter alia, a key role in the host cutaneous defense against S. aureus [22].…”

Section: Discussionmentioning

confidence: 99%

Influence of immune status on the airborne colonization of piglets with methicillin-resistant staphylococcus aureus (MRSA) clonal complex (CC) 398

Rosen¹,

Ebner²,

Schmidt³

et al. 2020

EuJMI

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Colonized vertebrates including humans and pigs are to date the main reservoirs of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). Currently, the mechanisms underlying colonization of pigs are not fully understood. We investigated the influence of piglet pre-immune status on airborne MRSA colonization. Three groups of MRSA-negative piglets were primed and exposed to airborne LA-MRSA (104 colony forming units (cfu)/m3) in an aerosol chamber for 24 h. One group was treated intramuscularly with dexamethasone (1 mg/kg body weight) to imitate weaning stress. The second group was exposed to bacterial endotoxin containing MRSA aerosol. Both conditions play a role in the development of multifactorial diseases and may promote MRSA colonization success. The third group served as control. The piglets' MRSA status was monitored for 21 days via swab samples. At necropsy, specific tissues and organs were analyzed. Blood was collected to examine specific immunological parameters. The duration of MRSA colonization was not extended in both treated groups compared to the control group, indicating the two immune-status influencing factors do not promote MRSA colonization. Blood sample analysis confirmed a mild dexamethasone-induced immune suppression and typical endotoxin-related changes in peripheral blood. Of note, the low-dose dexamethasone treatment showed a trend of increased MRSA clearance.

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Glucocorticoid dexamethasone down-regulates basal and vitamin D3 induced cathelicidin expression in human monocytes and bronchial epithelial cell line

Cited by 22 publications

References 23 publications

Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α

Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α

25-Hydroxyvitamin D<sub>3</sub> Alleviates Experimental Periodontitis via Promoting Expression of Cathelicidin in Mice with Type 2 Diabetic Mellitus

Influence of immune status on the airborne colonization of piglets with methicillin-resistant staphylococcus aureus (MRSA) clonal complex (CC) 398

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