Association of vitamin <scp>D</scp> and antimicrobial peptide production during late‐phase allergic responses in the lung

Liu, M. C.; Xiao, Huamei; Brown, Alex; Ritter, Cynthia S.; Schroeder, Johann O.

doi:10.1111/j.1365-2222.2011.03879.x

Cited by 31 publications

(29 citation statements)

References 37 publications

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“…We also demonstrate for the first time that the Th2 cytokine IL-13 increases vitamin D-induced expression of hCAP18/LL-37, most likely by increasing expression of the 25D 3 -activating CYP27B1. A recent study by Liu et al reported increased levels of LL-37, 1,25D3, and 25D3 in bronchoalveolar lavage (BAL) fluid from allergic subjects after segmental allergen challenge, which is in line with our observations (32). However, their observations could be partly explained by vascular leakage.…”

Section: Discussioncontrasting

confidence: 34%

Interleukin 13 Exposure Enhances Vitamin D-Mediated Expression of the Human Cathelicidin Antimicrobial Peptide 18/LL-37 in Bronchial Epithelial Cells

et al. 2012

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25D 3 ), by CYP27B1. Low circulating vitamin D levels in childhood asthma are associated with more-severe exacerbations, which are often associated with infections. Atopic asthma is accompanied by Th2-driven inflammation mediated by cytokines such as interleukin 4 (IL-4) and IL-13, and the effect of these cytokines on vitamin D metabolism and hCAP18/LL-37 expression is unknown. Therefore, we investigated this with well-differentiated bronchial epithelial cells. To this end, cells were treated with IL-13 with and without 25D 3 , and expression of hCAP18/LL-37, CYP27B1, the 1,25D 3 -inactivating enzyme CYP24A1, and vitamin D receptor was assessed by quantitative PCR. We show that IL-13 enhances the ability of 25D 3 to increase expression of hCAP18/LL-37 and CYP24A1. In addition, exposure to IL-13 resulted in increased CYP27B1 expression, whereas vitamin D receptor (VDR) expression was not significantly affected. The enhancing effect of IL-13 on 25D 3 -mediated expression of hCAP18/LL-37 was further confirmed using SDS-PAGE Western blotting and immunofluorescence staining.In conclusion, we demonstrate that IL-13 induces vitamin D-dependent hCAP18/LL-37 expression, most likely by increasing CYP27B1. These data suggest that Th2 cytokines regulate the vitamin D metabolic pathway in bronchial epithelial cells.T he upper respiratory tract is continuously exposed to pathogens. Epithelial cells function as the front line of host defense in the lung by preventing microbes from entering the bloodstream through the physical barrier provided by the tight junctions (24) and mucociliary clearance (36). Furthermore, epithelial cells secrete antimicrobial peptides and proteins (AMPs), such as lysozyme, lactoferrin and defensins, reactive oxygen and nitrogen species, interferons, and chemokines and cytokines, which eliminate pathogens directly or indirectly via attraction of phagocytic leukocytes (23, 55). In the lung, the AMP human cathelicidin (hCAP18/LL-37) is mainly secreted by neutrophils and epithelial cells, and the active peptide LL-37 displays broad-spectrum antimicrobial activity against bacteria, fungi, and viruses. It also contributes to microbial clearance by other mechanisms, including attraction of phagocytes (21, 48).In epithelial cells, a variety of stimuli, including proinflammatory cytokines (17, 22), microbial products (35), injury (15), endoplasmic reticulum (ER) stress (39), and butyrate, a short-chain fatty acid produced by resident colonic bacteria (41,44,44), have been shown to increase expression of hCAP18/LL-37. Recent studies also showed that vitamin D is an important regulator of hCAP18/LL-37 expression in epithelial cells and macrophages (56,58). Other studies showed that microbial exposures may also increase vitamin D-mediated expression of hCAP18/LL-37 through the induction of 25-hydroxy-vitamin D-1-␣-hydroxylase (CYP27B1), which converts 25-hydroxy-vitamin D 3 (25D 3 ) into the active 1,25(OH) 2 -vitaminD 3 (1,25D 3 ) (25,33).One of the well-established functions of vitamin D is mediating calcium ...

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Section: Discussioncontrasting

confidence: 34%

Interleukin 13 Exposure Enhances Vitamin D-Mediated Expression of the Human Cathelicidin Antimicrobial Peptide 18/LL-37 in Bronchial Epithelial Cells

et al. 2012

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“…There may be several other explanations for our differing observations. First, few data exist regarding the relationship between plasma and sputum cathelicidin [25], [26]. Second, prior studies have focused on patient populations with specific exposures, such as farmers, patients with cystic fibrosis, or smokers in acute care facilities [22], [23].…”

Section: Discussionmentioning

confidence: 99%

“…Our study did not have concurrent blood and bronchoalveolar cathelicidin measurements. Prior data reported an association between peripheral blood and BAL cathelicidin levels [25]. Multivitamin use was self-reported and is therefore subject to expectation and recall bias.…”

Section: Discussionmentioning

confidence: 99%

A Cross Sectional Analysis of the Role of the Antimicrobial Peptide Cathelicidin in Lung Function Impairment within the ALIVE Cohort

et al. 2014

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BackgroundVitamin D deficiency is associated with reduced lung function. Cathelicidin, an antimicrobial peptide regulated by vitamin D, plays a role within the innate immune system. The association of cathelicidin with lung function decrement and respiratory infection is undefined.We determined the independent relationship of cathelicidin with lung function.MethodsIn a cross-sectional analysis of 650 participants in an urban observational cohort with high smoking prevalence, plasma 25(OH)-vitamin D and cathelicidin levels were measured from stored samples obtained within 6 months of spirometry study visits. Multivariable linear regression was used to determine the independent association between low cathelicidin (defined as the lowest quartile of the cohort) and absolute forced expiratory volume in 1 second (FEV1).ResultsThe mean age of the cohort was 49 years; 91% were black, 35% female and 41% HIV-infected. Participants with low cathelicidin had a 183 mL lower FEV1 compared to higher cathelicidin (p = 0.009); this relationship was maintained (115 ml lower; p = 0.035) after adjusting for demographics, BMI, and smoking. Neither HIV serostatus, heavy smoking history, nor 25(OH)-vitamin D levels were associated with cathelicidin levels. Participants with low cathelicidin had a greater prevalence of prior bacterial pneumonia (21% versus 14%; p = 0.047). Inclusion of pneumonia in adjusted models did not substantially reduce the FEV1 decrement observed with low cathelicidin (104 mL lower FEV1; p = 0.05). Lung function decrements associated with low cathelicidin were greatest among individuals with lower 25(OH)-vitamin D levels.ConclusionsIn a cohort at risk for airflow obstruction, low cathelicidin was independently associated with lower FEV1. These clinical data support a mechanistic link between 25(OH)-vitamin D deficiency and lung function impairment, independent of pneumonia risk.

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“…There has been considerable interest in recent years in the potential role of vitamin D deficiency as a risk factor for a host of conditions including asthma and other allergic diseases [3][4][5]. We have recently reviewed this controversial literature and a potential role in food allergy is postulated in a review by Vuillermin and colleagues (pp.…”

Section: Vitamin D; the New Wonder Drug?mentioning

confidence: 99%

The Editor takes a closer look at some of this month's articles

2013

Clin Experimental Allergy

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The Editor takes a closer look at some of this month's articlesSmoking and asthma: amplification or suppression?As many asthmatics smoke as non-asthmatics, a testimony to the addictive effects of tobacco. Smoking asthmatics are generally regarded as more difficult to control than their nonsmoking counterparts and long-term smokers often have a mixed asthma-COPD picture. Decline in lung function is accelerated in asthmatic smokers. However, it is not clear if smoking amplifies, attenuates or just modifies airway inflammation, for example by promoting a more neutrophilic profile. It is sufficiently common for people to say that their respiratory problems started after they stopped smoking to raise the possibility that smoking may be having a suppressive effect on airway inflammation and airway hyperresponsiveness (AHR). Interestingly, Paul O'Byrne's group recently reported in the journal a reduced effect on AHR after allergen challenge, despite no obvious effect on airway inflammation [1]. Two studies in this issue have examined the effect of smoking on the immunology of asthma. Nagasaki and colleagues (pp. 608-615) found that smoking promoted a Th2 pattern of inflammation with more IgE, eosinophils, and TSLP in smoking asthmatics. Similarly, found increased levels of leukotrienes and PGE2 in the sputum of smoking asthmatics the former associated with eosinophils and the latter with neutrophils. Evidence from these two studies therefore supports the expected pro-inflammatory role of smoking in asthma.

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Association of vitamin D and antimicrobial peptide production during late‐phase allergic responses in the lung

Cited by 31 publications

References 37 publications

Interleukin 13 Exposure Enhances Vitamin D-Mediated Expression of the Human Cathelicidin Antimicrobial Peptide 18/LL-37 in Bronchial Epithelial Cells

Interleukin 13 Exposure Enhances Vitamin D-Mediated Expression of the Human Cathelicidin Antimicrobial Peptide 18/LL-37 in Bronchial Epithelial Cells

A Cross Sectional Analysis of the Role of the Antimicrobial Peptide Cathelicidin in Lung Function Impairment within the ALIVE Cohort

The Editor takes a closer look at some of this month's articles

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