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Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
An adipokine and an antimicrobial protein, this protein is known by several names: lipocalin 2 or siderocalin or neutrophil gelatinase (MMP9)-associated lipocalin (NGAL), human neutrophil lipocalin (HNL), 24p3, super-inducible protein 24 (SIP24), uterocalin, neu-related lipocalin (NRL), α2-microglobulin-related protein, and so forth. This 178-amino-acid-long protein may be found as a 24 kDa monomer, a 46 kDa disulfide-linked homodimer, or a disulfide-linked heterodimer with gelatinase B, that is, MMP9. Its strongest sources are neutrophils and kidney tubular cells when triggered by stress or cytokines. But it is also produced at low baseline levels in neutrophils, adipocytes, chondrocytes, endometrial cells, keratinocytes, macrophages, epithelial and endothelial cells, fibroblasts, vascular smooth muscle cells, hepatocytes, mesangial and microglial cells, pneumocytes, splenocytes, and thymocytes.
Drug discovery through the isolation of natural products from Burkholderia
Published in Expert Opinion on Drug Discovery, 2021
Adam Foxfire, Andrew Riley Buhrow, Ravi S. Orugunty, Leif Smith
In pathogenesis, Pch is critical in sequestering ferric iron from the host. In order to deter colonization, mammalian tissues have low-free iron content. Low free iron concentration is accomplished by the iron-binding protein transferrin and the secretory iron-binding protein lactoferrin [19]. Iron acquisition by pathogens is of such significance that mammals have developed a targeted immune protein known as siderocalin, which sequesters siderophores to prevent the acquisition of iron by pathogens. This reduces the ability of microbes to colonize tissues. However, Pch is a ‘stealth’ siderophore, meaning it is not sequestered by siderocalin, thus increasing the virulence of Bcc strains which produce the compound [19,24]. One study also found that in a rat model of chronic pulmonary infection, where Pch-negative Bcc strains were supplemented with Pch, the pathological involvement measured by area of the lungs increased two-fold. However, the number of bacteria recovered did not change against the control [33]. Evidence suggests iron bound to Pch could function as a catalyst for hydroxyl radical formation, which could be related to the increased tissue damage observed in the rat model and inflammation in humans [34]. Pch has recently been shown to also serve an important function in iron-rich conditions; it binds iron and prevents it from entering the cell by diffusion, staving off metal toxicity [22].
Anticalin® proteins: from bench to bedside
Published in Expert Opinion on Biological Therapy, 2021
Friedrich-Christian Deuschle, Elena Ilyukhina, Arne Skerra
To generate an Anticalin with prescribed ligand-binding function and, in case of therapeutic application, with pharmacologically useful properties, methods of targeted random mutagenesis in combination with powerful high-throughput selection have been developed. Since the inception of this technology (Figure 2), a series of natural lipocalin proteins were successfully employed for the selection of Anticalin proteins: the bilin-binding protein (BBP) from the butterfly Pieris brassicae, the human apolipoprotein D, the human tear lipocalin (Tlc, also known as lipocalin 1, Lcn1) and the human lipocalin 2 (Lcn2, also known as the neutrophil gelatinase-associated lipocalin, NGAL, or as siderocalin). The first Anticalins, which were based on the BBP, were selected against the haptens fluorescein [11] and digitalis [16], serving as a proof of concept for the technology as well as providing useful bioanalytical binding reagents. The anti-fluorescein Anticalin was later applied as a fusion protein with two copies of an scFv antibody fragment specific for the extra-domain A (ED-A) of fibronectin, a marker of tumor angiogenesis. This fusion protein was successfully used for the in vivo pretargeting/imaging of solid tumors in a mouse model after subsequent administration of a conjugate between fluorescein and a near-infrared fluorescent dye [17].
Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron
Published in Gut Microbes, 2020
Piu Saha, Beng San Yeoh, Xia Xiao, Rachel M. Golonka, Ahmed A. Abokor, Camilla F. Wenceslau, Yatrik M. Shah, Bina Joe, Matam Vijay-Kumar
Besides functioning as an iron chelator, Ent also benefits their producers through other non-canonical functions such as facilitating bacterial colonization,17 quorum sensing and biofilm formation,18 and mitigating oxidative stress.19-21 In addition, we have shown that Ent can impede neutrophil functions by inhibiting myeloperoxidase22,23 and the formation of neutrophil extracellular traps.16 To thwart the negative effects of Ent, the host synthesizes the innate immune protein lipocalin 2 (Lcn2; alias neutrophil gelatinase-associated lipocalin [NGAL], siderocalin, or 24p3) to sequester both iron-bound and iron-free Ent.24 Such maneuver has been shown to be a potent host defense against intestinal25 and lung26 infections by Ent-producing Enterobacteriaceae. Previous studies have also shown that lung epithelia secrete interleukin 8 (IL-8) in response to Ent alone or in combination with Lcn2.27,28 However, it remains unclear as to whether such a response could be recapitulated in IECs, which are more likely to be exposed to Ent-producing gut commensals under normal physiological conditions and in the absence of infection.