scholarly journals Melanogenesis Connection with Innate Immunity and Toll-Like Receptors

2020 ◽  
Vol 21 (24) ◽  
pp. 9769
Author(s):  
Saaya Koike ◽  
Kenshi Yamasaki

The epidermis is located in the outermost layer of the living body and is the place where external stimuli such as ultraviolet rays and microorganisms first come into contact. Melanocytes and melanin play a wide range of roles such as adsorption of metals, thermoregulation, and protection from foreign enemies by camouflage. Pigmentary disorders are observed in diseases associated with immunodeficiency such as Griscelli syndrome, indicating molecular sharing between immune systems and the machineries of pigment formation. Melanocytes express functional toll-like receptors (TLRs), and innate immune stimulation via TLRs affects melanin synthesis and melanosome transport to modulate skin pigmentation. TLR2 enhances melanogenetic gene expression to augment melanogenesis. In contrast, TLR3 increases melanosome transport to transfer to keratinocytes through Rab27A, the responsible molecule of Griscelli syndrome. TLR4 and TLR9 enhance tyrosinase expression and melanogenesis through p38 MAPK (mitogen-activated protein kinase) and NFκB signaling pathway, respectively. TLR7 suppresses microphthalmia-associated transcription factor (MITF), and MITF reduction leads to melanocyte apoptosis. Accumulating knowledge of the TLRs function of melanocytes has enlightened the link between melanogenesis and innate immune system.

2008 ◽  
Vol 25 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Beena Mailaparambil ◽  
Marcus Krueger ◽  
Jessica Heinze ◽  
Johannes Forster ◽  
Andrea Heinzmann

Toll like receptors (TLRs) are an essential part of the innate immune response. So far, ten different TLRs were identified in humans. They recognize a wide range of microbial and viral pathogens. Infection by respiratory syncytial virus (RSV) is still a major health problem, about 2% of all children are hospitalised due to RSV bronchiolitis during their first 2 years of live. TLR4 has already been described in association with RSV associated diseases by us and others.Thus we were interested whether other TLRs are also involved in the genetics of severe RSV infection. We genotyped 19 polymorphisms in the autosomal TLRs, these are TLR1, 2, 3, 5, 6, 9 and 10. Association analyses by the Armitage's Trend test revealed weak association of one TLR9 promoter polymorphism with RSV infection (p= 0.013). In addition, association was found with TLR10 haplotypes (p= 0.024).We conclude from our data – that – although we can not rule out a minor involvement ofTLR9polymorphism andTLR10haplotypes – TLRs other than TLR4 do not play a major role in the genetics of severe RSV associated diseases. Future studies should focus on additional genes of the innate immune response.


2016 ◽  
pp. 126-129
Author(s):  
M. Makarenko ◽  
◽  
D. Hovsyeyev ◽  
L. Sydoryk ◽  
◽  
...  

Different kinds of physiological stress cause mass changes in the cells, including the changes in the structure and function of the protein complexes and in separate molecules. The protein functions is determined by its folding (the spatial conclusion), which depends on the functioning of proteins of thermal shock- molecular chaperons (HSPs) or depends on the stress proteins, that are high-conservative; specialized proteins that are responsible for the correct proteinaceous folding. The family of the molecular chaperones/ chaperonins/ Hsp60 has a special place due to the its unique properties of activating the signaling cascades through the system of Toll-like receptors; it also stimulates the cells to produce anti- inflammatory cytokines, defensins, molecules of cell adhesion and the molecules of MHC; it functions as the intercellular signaling molecule. The pathological role of Hsp60 is established in a wide range of illnesses, from diabetes to atherosclerosis, where Hsp60 takes part in the regulation of both apoptosis and the autoimmune processes. The presence of the HSPs was found in different tissues that are related to the reproductive system. Key words: molecular chaperons (HSPs), Toll-like receptors, reproductive function, natural auto antibody.


2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 


2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek

Malaria parasites, Plasmodium can infect a wide range ofhosts including humans and rodents. There are two copies ofmitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise ofpresented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series ofpublicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localizedandcontain both a nuclear localization signal (NLS) anda Leucine-rich nuclear export signal (NES). The activation motifs ofTDYand TSH werefound to befully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection ofa multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising ofdifferent amino acids present in MAPK1 and MAPK2 respectively, with respect to rodent and human Plasmodia. 1t is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs.


Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 72
Author(s):  
Lena Trifonov ◽  
Vadim Nudelman ◽  
Michael Zhenin ◽  
Guy Cohen ◽  
Krzysztof Jozwiak ◽  
...  

TLR4, a member of the toll-like receptors (TLRs) family, serves as a pattern recognition receptor in the innate immune response to different microbial pathogens. [...]


2021 ◽  
Vol 43 (1) ◽  
pp. 36-51
Author(s):  
Alicja Ponder ◽  
Ewelina Hallmann ◽  
Martyna Kwolek ◽  
Dominika Średnicka-Tober ◽  
Renata Kazimierczak

Anthocyanins are widely distributed secondary metabolites that play an essential role in skin pigmentation of many plant organs and microorganisms. Anthocyanins have been associated with a wide range of biological and pharmacological properties. They are also effective agents in the prevention and treatment of many chronic diseases. Berries are particularly abundant in these compounds; therefore, their dietary intake has health-promoting effects. The aim of this study was to identify and determine the anthocyanin content in selected species and cultivars of berry fruits, such as raspberry, blackberry, red currant, blackcurrant, and highbush blueberry, widely consumed by Europeans. The concentrations of anthocyanins were determined by HPLC, identifying individual compounds: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside, delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-rutinoside, delphinidin-3-O-galactoside, cyanidin-3-O-galactoside, and malvidin-3-O-galactoside. The experimental data showed that the selected species and cultivars of berry fruits differ significantly in the contents of anthocyanins. Among all species tested, blackberry and blackcurrant were characterized significantly by the highest content of anthocyanins (sum), while the lowest content was found in red currant fruits. Additionally, the content of individual anthocyanin compounds in particular species and cultivars was also different. Considering the high content of anthocyanins and their potential positive impact on human health and protection against disease, berries should be part of healthy nutrition.


2006 ◽  
Vol 74 (8) ◽  
pp. 4430-4438 ◽  
Author(s):  
Kaushik Chakrabarty ◽  
Wenxin Wu ◽  
J. Leland Booth ◽  
Elizabeth S. Duggan ◽  
K. Mark Coggeshall ◽  
...  

ABSTRACT Contact with the human alveolar macrophage plays a key role in the innate immune response to Bacillus anthracis spores. Because there is a significant delay between the initial contact of the spore with the host and clinical evidence of disease, there appears to be temporary containment of the pathogen by the innate immune system. Therefore, the early macrophage response to Bacillus anthracis exposure is important in understanding the pathogenesis of this disease. In this paper, we studied the initial events after exposure to spores, beginning with the rapid internalization of spores by the macrophages. Spore exposure rapidly activated the mitogen-activated protein kinase signaling pathways extracellular signal-regulated kinase, c-Jun-NH2-terminal kinase, and p38. This was followed by the transcriptional activation of cytokine and primarily monocyte chemokine genes as determined by RNase protection assays. Transcriptional induction is reflected at the translational level, as interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) cytokine protein levels were markedly elevated as determined by enzyme-linked immunosorbent assay. Induction of IL-6 and TNF-α, and, to a lesser extent, IL-1α and IL-1β, was partially inhibited by the blockade of individual mitogen-activated protein kinases, while the complete inhibition of cytokine induction was achieved when multiple signaling pathway inhibitors were used. Taken together, these data clearly show activation of the innate immune system in human alveolar macrophages by Bacillus anthracis spores. The data also show that multiple signaling pathways are involved in this cytokine response. This report is the first comprehensive examination of this process in primary human alveolar macrophages.


2005 ◽  
Vol 16 (12) ◽  
pp. 5538-5550 ◽  
Author(s):  
James M. Mullin ◽  
James M. Leatherman ◽  
Mary Carmen Valenzano ◽  
Erika Rendon Huerta ◽  
Jon Verrechio ◽  
...  

Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK1 renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of d-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to d-mannitol (Mr 182), polyethylene glycol (Mr 4000), and 10,000-Mr methylated dextran but not to 2,000,000-Mr methylated dextran. This implies a “ceiling” on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier.


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