The Combined Effect of Azithromycin and Insulin-Like Growth Factor-1 on Cultured Human Meibomian Gland Epithelial Cells

Liu, Yang; Ding, Juan

doi:10.1167/iovs.14-14782

Cited by 22 publications

(16 citation statements)

References 32 publications

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“…Androgens have been reported to increase the production of IGF-1 [86, 87], upregulate IGF-1 receptor expression [88, 89], and modulate IGF-1 signaling [90]. IGF-1, in turn, is known to stimulate the function of human meibomian gland epithelial cells [91, 92]. Consequently, androgen deficiency could result in a loss of IGF-1 activity, which is known to be associated with the development of DED [93].…”

Section: Discussionmentioning

confidence: 99%

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome

et al. 2018

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Purpose: We hypothesized that women with primary (pSS) and secondary Sjögren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis. Methods: Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sjögren’s Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women’s Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED). Results: Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased ∼10-fold in all pSS, sSS, and MGD groups relative to controls. Conclusions: Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED.

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Section: Discussionmentioning

confidence: 99%

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome

et al. 2018

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“…This effect might explain how the ω-FAs enhanced AZM’s impact on neutral lipid accumulation, given that AZM typically elevates the IHMGEC levels of cholesterol, cholesterol ester and phospholipids, but reduces those of triglycerides. 19,21,22 The ω-FAs may have countered the AZM-induced loss of triglyceriedes, leading to increased LipidTox staining of the IHMGECs. In contrast, the ω-FAs appeared to decrease the AZM-induced generation of lysosomes, as identified by LysoTracker.…”

Section: Discussionmentioning

confidence: 99%

“…Azithromycin (AZM, 10 μg/ml; Santa Cruz Biotechnology) was used as a positive control in all experiments, because this antibiotic has well-defined effects on both the proliferation and differentiation of IHMGECs. 19–22 Following treatment, cells were processed for enumerative, histological and biochemical procedures.…”

Section: Methodsmentioning

confidence: 99%

“…lysosomes), as previously reported. 19–22 The cellular content of free and esterified cholesterol, triglycerides, phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol were determined by high-performance thin-layer chromatography (HPTLC; Silica Gel 60, Merck, Darmstadt, Germany), as described. 20,22 The cellular lysate levels of Lamp-1 and LC3 proteins, which are biomarkers for lysosomes and autophagosomes 23,24 , were assessed by Western blots.…”

Section: Methodsmentioning

confidence: 99%

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Influence of Omega 3 and 6 Fatty Acids on Human Meibomian Gland Epithelial Cells

Liu

Kam

Sullivan

2016

Cornea

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Purpose Oral supplementation with omega 3 (ω-3) and/or 6 (ω-6) fatty acids (FAs) has been reported to alleviate the signs and symptoms of dry eye disease (DED), and to improve the expressibility and quality of meibum, in patients with meibomian gland dysfunction (MGD). We tested our hypothesis that these FA effects may reflect a direct FA action on human meibomian gland epithelial cells (HMGECs). Methods Immortalized (I) HMGECs were cultured with ω-3, ω-6 or both FAs together for up to 7 days in the presence or absence of serum. Following FA exposure, cells were analyzed for lipid expression, lysosome content and proliferative ability. Results Our research shows that ω-3 and ω-6 stimulate the accumulation of small neutral lipid-containing vesicles, but not lysosomes, in IHMGECs. This vesicular effect was associated with a 2.4- to 3.7-fold increase in the cellular content of triglycerides following ω-3 and ω-6 treatment, respectively. The combination of both FAs together also enhanced triglyceride levels. Of interest, culture of IHMGECs with ω-3 and azithromycin (AZM), a known inducer of IHMGEC differentiation, led to a significantly greater amount of total neutral lipids, relative to that found with AZM alone. Cellular exposure to the FAs did not alter the expression of free or esterified cholesterol, or phospholipids. Further, these FAs, alone or together, prevented the proliferation of IHMGECs in serum-free, but not serum-containing, media. Conclusions Our findings support our hypothesis and demonstrate that ω-3 and ω-6 can act directly on IHMGECs to influence the quality and quantity of intracellular lipids.

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“…Total cellular lipid composition was analyzed by high performance thin-layer chromatography (HPTLC). 12 Each sample contained the same amount of cellular extract, and cell lysates were analyzed by immunoblot. Membranes were incubated with antibodies specific for SREBP-1 (Santa Cruz, H-160, 1:500), cyclin B1 (Cell Signaling Technology, Danvers, MA; 1:500) or β-actin (Cell Signaling Technology, 1:10,000), followed by HRP-conjugated secondary antibodies (1:5,000, Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Can Tetracycline Antibiotics Duplicate the Ability of Azithromycin to Stimulate Human Meibomian Gland Epithelial Cell Differentiation?

Liu

Kam

Ding

et al. 2015

Cornea

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Purpose Azithromycin and tetracyclines are commonly prescribed in the United States for the treatment of meibomian gland dysfunction (MGD). The efficacy of these antibiotics has been thought to be their anti-inflammatory and anti-bacterial actions, which suppress MGD-associated posterior blepharitis and growth of lid bacteria. However, we recently discovered that azithromycin can act directly on human meibomian gland epithelial cells (HMGECs) to stimulate their function. In this study we sought to determine whether tetracycline antibiotics can duplicate this azithromycin effect. Methods Immortalized HMGEC were cultured in the presence of vehicle, azithromycin, doxycycline, minocycline or tetracycline for 5 days. Cells were evaluated for cholesterol and neutral lipid staining and the lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography. Results Our results demonstrate that azithromycin’s ability to stimulate the differentiation of human meibomian gland cells is unique, and is not duplicated by doxycycline, minocycline or tetracycline. Azithromycin, but not the other antibiotics, significantly increased the cellular accumulation of cholesterol, cholesterol esters, phospholipids and lysosomes. These differentiative actions of azithromycin were paralleled by an increased expression of sterol regulatory element-binding protein 1. Conclusions Our findings show that the stimulatory effects of azithromycin on human meibomian gland epithelial cell function are unique, and not duplicated by the antibiotics doxycycline, minocycline or tetracycline. Our results further suggest that this stimulatory influence of azithromycin may contribute to its beneficial effect in treating MGD and its associated evaporative dry eye disease.

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The Combined Effect of Azithromycin and Insulin-Like Growth Factor-1 on Cultured Human Meibomian Gland Epithelial Cells

Abstract: Our results support our hypothesis, and this combination regime may represent a unique and effective treatment of MGD.

Cited by 22 publications

References 32 publications

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome

Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome

Influence of Omega 3 and 6 Fatty Acids on Human Meibomian Gland Epithelial Cells

Can Tetracycline Antibiotics Duplicate the Ability of Azithromycin to Stimulate Human Meibomian Gland Epithelial Cell Differentiation?

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