Expression of Neutrophil Gelatinase-Associated Lipocalin in Skin Epidermis

Seo, Seong Jun; Ahn, Jiyoung; Hong, Chang-Kwun; Seo, Eun-Young; Kye, Kyung-Chae; Lee, Woonghee; Lee, Sangkeun; Lim, Jong-Soon; Hahn, Myong‐Joon; Kjeldsen, Lars; Borregaard, Niels; Kim, Chang Deok; Park, Jang-Kyu; Lee, Jeung‐Hoon

doi:10.1038/sj.jid.5700035

Cited by 24 publications

(28 citation statements)

References 13 publications

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“…NGAL is believed to kill bacteria by sequestering iron that is bound to a bacterial siderophore, thus, depriving bacteria of iron that is essential for its survival (7). NGAL expression has been reported within the infundibulum of the hair follicle and follicular epithelium in normal human skin (31,32). We failed, however, to detect NGAL expression in follicles from acne patients prior to isotretinoin therapy.…”

Section: Discussioncontrasting

confidence: 46%

Neutrophil gelatinase–associated lipocalin mediates 13-cis retinoic acid–induced apoptosis of human sebaceous gland cells

Nelson¹,

Zhao²,

Gilliland³

et al. 2008

J. Clin. Invest.

131

141

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13-cis retinoic acid (13-cis RA; also known as isotretinoin) is the most potent agent available for treatment of acne. It is known that the drug induces apoptosis in cells cultured from human sebaceous glands, but its mechanism of action has not been determined. In this study, skin biopsies were taken from 7 patients with acne prior to and at 1 week of treatment with 13-cis RA. TUNEL staining confirmed that 13-cis RA induced apoptosis in sebaceous glands. Transcriptional profiling of patient skin and cultured human sebaceous gland cells (SEB-1 sebocytes) indicated that lipocalin 2 was among the genes most highly upregulated by 13-cis RA. Lipocalin 2 encodes neutrophil gelatinase-associated lipocalin (NGAL), which functions in innate immune defense and induces apoptosis of murine B lymphocytes. Increased immunolocalization of NGAL was noted in patients' sebaceous glands following treatment with 13-cis RA, and recombinant NGAL induced apoptosis in SEB-1 sebocytes. Furthermore, apoptosis in response to 13-cis RA was inhibited in the presence of siRNA to lipocalin 2. These data indicate that NGAL mediates the apoptotic effect of 13-cis RA and suggest that agents that selectively induce NGAL expression in sebaceous glands might represent therapeutic alternatives to the use of 13-cis RA to treat individuals with acne.

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Section: Discussioncontrasting

confidence: 46%

Neutrophil gelatinase–associated lipocalin mediates 13-cis retinoic acid–induced apoptosis of human sebaceous gland cells

Nelson¹,

Zhao²,

Gilliland³

et al. 2008

J. Clin. Invest.

131

141

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“…More recently, expression of NGAL was evaluated as a biomarker for nephritis in childhood-onset systemic lupus erythematosus, and was found to correlate with renal disease activity and renal damage (21). In the epidermis, expression of NGAL has been found to be localized to the hair follicle compartments in normal tissue, particularly to the inner root sheath and infundibulum, and to be up-regulated in psoriatic skin lesions (22).…”

mentioning

confidence: 99%

Neutrophil gelatinase–associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9

Gupta¹,

Shukla²,

Cowland³

et al. 2007

Arthritis & Rheumatism

121

119

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Objective. Expression of matrix metalloproteinase 9 (MMP-9) is up-regulated in osteoarthritis (OA) and usually presents as multiple bands when synovial fluid (SF) from OA patients is analyzed by zymography. Among these bands is an ϳ125-130-kd band for high molecular weight (HMW) gelatinase, which has not been characterized. This study was undertaken to characterize the HMW MMP activity in OA SF.Methods. MMP activity in OA SF was determined by gelatin zymography. Recombinant MMPs were used to identify MMP activity on the zymogram. Western immunoblotting, immunoprecipitation, and immunodepletion analyses were performed using antibodies specific for human MMP-9 and human neutrophil gelatinase-associated lipocalin (NGAL). Human cartilage matrix degradation was determined by dimethylmethylene blue assay.Results. Zymographic analysis showed that the HMW gelatinase in OA SF comigrated with a purified NGAL-MMP-9 complex. Results of Western immunoblotting showed that the HMW gelatinase was also recognized by antibodies specific for human NGAL or human MMP-9. These same antibodies also immunoprecipitated the HMW gelatinase activity from OA SF. The NGAL-MMP-9 complex was reconstituted in vitro in gelatinase buffer. In the presence of NGAL, MMP-9 activity was stabilized; in the absence of NGAL, rapid loss of MMP-9 activity occurred. MMP-9-mediated release of cartilage matrix proteoglycans was significantly higher in the presence of NGAL (P < 0.05).Conclusion. Our findings demonstrate that the HMW gelatinase activity in OA SF represents a complex of NGAL and MMP-9. The ability of NGAL to protect MMP-9 activity is relevant to cartilage matrix degradation in OA and may represent an important mechanism by which NGAL may contribute to the loss of cartilage matrix proteins in OA.The developed world's aging population has experienced a dramatic increase in the incidence of joint dysfunction and osteoarthritis (OA), leading to a compromised quality of life. Aging, biomechanical stress, and oxidative stress, in addition to genetic factors and trauma, all appear to be associated with degenerative and progressive cartilage and bone changes in OA, particularly in the weight-bearing joints. Although OA is not considered an inflammatory disease by traditional standards, elevated levels of proinflammatory cytokines, such as interleukin-1␤ (IL-1␤) and tumor necrosis factor ␣, have been observed in OA synovial fluid (SF), supporting the notion that there is an inflammatory component associated with the pathogenesis of OA (for review, see refs. 1-3).The only cell type present in articular cartilage is the chondrocyte, which is embedded within an extracellular matrix (ECM) primarily composed of type II collagen and aggrecan. Chondrocytes arise from a mesenchymal progenitor cell and are responsible for the biosynthesis of ECM proteins and their transport into the space occupied by the ECM. Chondrocytes play an important role in cartilage homeostasis by maintaining the proper balance between anabolic pathways, which Supported in part by the NIH...

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“…Son zamanlarda farklı inflamatuvar deri hastalıkları ve kanserlerde, LCN2 ve onun patogenezdeki rolünü araştıran çok sayıda araştırma yapılmıştır (4,5,9,(12)(13)(14)(15). Çalışmamızda, LCN2, psoriasis patogenezinde yer alabilecek bir antimikrobiyal protein olması ve aynı zamanda hastalık komorbiditelerinden metabolik sendrom bulgularıyla ilişkilendirilmesi nedeniyle, immünohistokimyasal olarak incelenmiştir.…”

Section: Discussionunclassified

“…Bu ekspresyonun kıl follikülüne mikroorganizmaların girişini engellediği ya da follikül keratinizasyonundaki fizyolojik rolüne bağlı olduğu düşünülmektedir (5,9). Çalışmamızda, iyi gelişmiş psoriatik lezyonlu olan ve kıl follikülü izlenen hastalarda ve kontrol grubunun yarısında yüzeye yakın kıl follikülü iç kılıfında LCN2 ekspresyonu görülmüştür.…”

Section: Discussionunclassified

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Immunohistochemical Detection of Lipocalin 2 Specific Receptor in Psoriasis

Sayar¹,

Özyurt²,

Karabulut³

et al. 2015

tdd

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Amaç: Serum Lipokalin 2 (LCN2) seviyelerinin psoriasiste artmış inflamasyon için bir genel belirteç olduğu bilinmektedir. Bu çalışmada, LCN2'nin psoriatik lezyonlardaki reseptör düzeyini araştırmayı amaçladık. Yöntemler: LCN2 immünohistokimyasal ekspresyonu, 31 psoriasis hastası ve 31 kontrol grubuna ait deri biyopsi örneklerinde araştırılmış ve sonuçlar guruplar arasında karşılaştırılmıştır. Bulgular: Hasta grubunda 19 (%61,3) plak psoriasisli hasta vardı ve bunların tamamında orta ve kuvvetli boyanma şiddetinde üst epidermal tabakada LCN2 immünohistokimyasal ekspresyonu saptanmıştır. Geriye kalan 12 hastada (%38,7) patolojik bulgulara göre, erken evre psoriatik lezyonları olan ve kontrol grubu biyopsilerinde epidermal LCN2 immünohistokimyasal ekspresyonu görülmemiştir. Kıl folliküllerinin iç kök kılıfında, LCN2 immünohistokimyasal ekspresyonu her iki gurupta da görüldü ve ekspresyonlar arasında istatistiksel anlamlı fark bulunamamıştır (p=1,00). Sonuç: Çalışmamızda, plak psoriasisli hastalarda üst epidermiste orta ve kuvvetli boyanma şiddetinde LCN2 immünohistokimyasal ekspresyonu tespit edilmiştir. Fakat kontrol grubu deri biyopsilerinde LCN2 immünohistokimyasal ekspresyonu epidermisde görülmemiştir. Bu bulgular, LCN2'nin psoriasis patogenezindeki önemine işaret edebilir. Öte yandan erken evre psoriatik lezyonları olan hastalarda ekspresyon saptanmaması LCN2'nin psoriasis patogenezinin ileri dönemlerinde etkin olduğunu düşündürmektedir. Objective: Serum Lipocalin 2 (LCN2) levels are a general indicator for increased inflammation in the patients with psoriasis. In this study, we aimed to investigate the receptor levels of LCN2 in psoriatic lesions. Methods: Immunohistochemical expression of LCN2 was investigated in 31 skin biopsy samples of patients with psoriasis and 31 skin biopsies of control group and the results were compared between the groups. Results: Among patient group, 19 patients (61.3%) had plaque psoriasis and in all of these, medium to strong staining intensity of LCN2 immunohistochemical expression was detected in the upper epidermal layer. In remaining 12 patients (38.7%) with pathologically early stage psoriatic lesions and control group epidermal LCN2 immunohistochemical expression was not observed. LCN2 immunohistochemical expression was detected in the inner root sheath of the hair follicles in both groups without any statistically difference (p=1.00). Conclusion:In our study, medium to strong staining of LCN2 receptor was detected in the superficial epidermis of the psoriatic plaques. But LCN2 immunohistochemical staining was not observed in control skin biopsies. These findings may point out the significance of LCN2 in pathogenesis of psoriasis. On the other hand, absence of expression in patients with early psoriatic lesions imply that LCN2 may be active at the later stages of the pathology.

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Expression of Neutrophil Gelatinase-Associated Lipocalin in Skin Epidermis

Cited by 24 publications

References 13 publications

Neutrophil gelatinase–associated lipocalin mediates 13-cis retinoic acid–induced apoptosis of human sebaceous gland cells

Neutrophil gelatinase–associated lipocalin mediates 13-cis retinoic acid–induced apoptosis of human sebaceous gland cells

Neutrophil gelatinase–associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9

Immunohistochemical Detection of Lipocalin 2 Specific Receptor in Psoriasis

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