Biomedical subjects

Jenny Kim

Publications and source records attributed to Jenny Kim.

11 recordsLinked to original sources

PubMed2006

Bcl-2-positive epidermal dendritic cells in inverted follicular keratoses but not squamous cell carcinomas or seborrheic keratoses.

AIM: In our previous research, bcl-2-positive dendritic cells were seen in increased numbers in suprabasal areas of inverted follicular keratoses (IFKs) compared to seborrheic keratoses (SKs). The purpose of this study was twofold; firstly, to support that these dendritic cells are Langerhans cells and secondly, to contrast the epidermal dendritic cells in IFKs, squamous cell carcinomas (SCCs), and SKs. METHODS: Ten IFKs and five SKs previously showing bcl-2-positive dendritic cells within the epidermis were stained with CD1a. Fifteen other IFKs were stained with CD1a alone. Ten SCCs were stained with bcl-2 and CD1a. RESULTS: In the 10 IFKs stained with both bcl-2 and CD1a, the density of CD1a-positive cells correlated well with the density of bcl-2-positive dendritic cells; in the five SKs, the density of CD1a-positive cells was similar to that seen in IFKs but was higher compared to the density of bcl-2-positive dendritic cells in SKs (p < 0.05). The IFKs had a significantly higher number of CD1a-positive cells compared to SCCs (p < 0.01). SCCs showed bcl-2-positive cells only within the basal layer of the normal epidermis flanking the carcinomas. CONCLUSIONS: These results suggest that there is different bcl-2 regulation of CD1a-positive cells in IFKs, SKs, and SCCs.

Antigens, CD1↗

PubMed2005

TGF-alpha regulates TLR expression and function on epidermal keratinocytes.

The expression of TLRs on epithelial cells provides a first line of defense against invading pathogens. We investigated the regulated expression and function of TLR5 and TLR9 on human keratinocytes, because we found by immunohistochemistry that these TLRs are expressed in distinct layers of the epidermis. We found that TGF-alpha, a growth and differentiation factor that is present during wound healing and in psoriasis, increased the expression of both TLR5 and TLR9 on keratinocytes. In addition, TGF-alpha regulated the function of TLR5 and TLR9, because activation with their respective ligands enhanced the production of IL-8 and human beta-defensins. These findings provide evidence that TGF-alpha up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces.

Adjuvants, Immunologic↗

PubMed2005

Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function.

A major consequence of microbial infection is the tissue injury that results from the host inflammatory response. In acne, inflammation is due in part to the ability of Propionibacterium acnes to activate TLR2. Because all-trans retinoic acid (ATRA) decreases inflammation in acne, we investigated whether it regulates TLR2 expression and function. Treatment of primary human monocytes with ATRA led to the down-regulation of TLR2 as well as its coreceptor CD14, but not TLR1 or TLR4. The ability of a TLR2/1 ligand to trigger monocyte cytokine release was inhibited by pre- and cotreatment with ATRA; however, TLR4 activation was affected by cotreatment only. ATRA also down-regulated monocyte cytokine induction by P. acnes. These data indicate that ATRA exerts an anti-inflammatory effect on monocytes via two pathways, one specifically affecting TLR2/1 and CD14 expression and one independent of TLR expression. Agents that target TLR expression and function represent a novel strategy to treat inflammation in humans.

Acne Vulgaris↗

PubMed2005

The role of toll-like receptors in the pathophysiology of acne.

Acne vulgaris is a common cutaneous disorder of the pilosebaceous follicle, affecting more than 45 million people in the United States alone. The pathogenesis of acne is multifactorial, involving abnormal hyperkeratinization, increased sebum production, hormones, cutaneous microbes, and immunological mechanisms. Many of the immunological processes that contribute to the formation of acne lesions take place at the very site of disease, the skin. Skin is an important component of the innate immune system, providing both physical barriers and rapid cellular responses by keratinocytes, Langerhans cells, and other infiltrating inflammatory cells. In this review, we discuss the ability of the innate immune system to use Toll-like receptors (TLRs) to recognize microbial patterns and initiate immune responses in cutaneous disorders. Because TLRs are vital players in infectious and inflammatory diseases, they are potential therapeutic targets. Indeed, the ability of TLRs to combat disease already has been harnessed through the development of drugs that act as TLR agonists. A better understanding of TLRs will allow for the development of new therapeutic options for cutaneous inflammatory diseases such as acne.

Acne Vulgaris↗

PubMed2005

The role of toll-like receptors in the pathogenesis and treatment of dermatological disease.

Toll-like receptors (TLR) are crucial players in the innate immune response to microbial invaders. These receptors are expressed on immune cells, such as monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are not only expressed by peripheral blood cells, but their expression has been demonstrated in airway epithelium and skin, important sites of host-pathogen interaction. Host cells expressing TLR are capable of recognizing conserved pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA, and their activation triggers signaling pathways that result in the expression of immune response genes and cytokine production. As TLR are instrumental in both launching innate immune responses and influencing adaptive immunity, regulation of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may be important in the pathophysiology of these diseases. Furthermore, since TLR are vital players in infectious and inflammatory diseases, they have been identified as potential therapeutic targets. Indeed, synthetic TLR agonists such as imiquimod have already established utility in treating viral pathogens and skin cancers. In the future, it seems possible there may also be drugs capable of blocking TLR activation and thus TLR-dependent inflammatory responses, providing new treatment options for inflammatory diseases.

Gene Expression Regulation↗

PubMed2005

Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against Propionibacterium acnes.

Propionibacterium acnes is a key therapeutic target in acne, yet this bacterium has become resistant to standard antibiotic agents. We investigated whether the human antimicrobial protein granulysin is a potential candidate for the treatment of acne. Granulysin and synthetic granulysin-derived peptides possessing a helix-loop-helix motif killed P. acnes in vitro. Modification of a helix-loop-helix peptide, 31-50, by substitution of a tryptophan for the valine at amino acid 44 (peptide 31-50v44w) to increase its interaction with bacterial surfaces also increased its antimicrobial activity. Moreover, when synthesized with D- rather than L-type amino acids, this peptide (D-31-50v44w) became less susceptible to degradation by proteases and more effective in killing P. acnes. Granulysin peptides were bactericidal, demonstrating an advantage over standard bacteriostatic antibiotics in their control of P. acnes. Moreover, peptide D-31-50v44w killed P. acnes in isolated human microcomedone preparations. Importantly, peptides 31-50, 31-50v44w, and D-31-50v44w also have potential anti-inflammatory effects, as demonstrated by suppression of P. acnes-stimulated cytokine release. Taken together, these data suggest that granulysin peptides may be useful as topical therapeutic agents, providing alternatives to current acne therapies.

Acne Vulgaris↗

PubMed2005

Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses.

Acne vulgaris is a common disorder that affects 40-50 million people in the USA alone. The pathogenesis of acne is multifactorial, including hormonal, microbiological and immunological mechanisms. One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). TLRs are pattern recognition receptors that recognize pathogen-associated molecular patterns conserved among microorganisms and elicit immune responses. We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Using transfectant cells we found that TLR2 was sufficient for NF-kappaB activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes.P. acnes induced activation of IL-12 and IL-8 production by primary human monocytes, and this cytokine production was inhibited by anti-TLR2-blocking antibody. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for the treatment of this common skin disease.

Acne Vulgaris↗

PubMed2003

PIASx is a transcriptional co-repressor of signal transducer and activator of transcription 4.

In response to interleukin 12 (IL-12) stimulation, a latent cytoplasmic transcription factor, Stat4 (signal transducer and activator of transcription 4), becomes tyrosine-phosphorylated and translocates into the nucleus where it binds to DNA to activate transcription. Cofactors that can directly bind and regulate Stat4 activity have not been described. We report here that PIASx, a member of the protein inhibitor of activated STAT (PIAS) family, is a negative regulator of Stat4. PIASx becomes associated with Stat4 following IL-12 stimulation in vivo. PIASx inhibits IL-12-stimulated and Stat4-dependent gene activation in human T cells. PIASx does not inhibit the DNA binding activity of Stat4. Instead PIASx is present in the Stat4-DNA binding complex. Finally the inhibitory activity of PIASx on Stat4-mediated gene activation is abolished by the histone deacetylase inhibitor trichostatin A. Our results suggest that PIASx may function as a co-repressor of Stat4.

Animals↗

PubMed2003

Update on pathogenesis and treatment of acne.

Acne vulgaris is a common cutaneous disorder of the pilosebaceous follicle. More than 45 million people are affected with acne vulgaris. In addition, 80% of people in the United States report that they suffered from acne at one point in life. It is estimated that US consumers spend $1.2 billion each year for the treatment of acne. Typically, lesions are pleomorphic and range from open and closed comedones to inflammatory papules, pustules, cysts, and nodules, and scarring may result. The disease is important, with a significant effect on patients' self-esteem. The pathogenesis is only partially understood and is multifactorial. Successful management of acne requires an understanding of the pathophysiology of disease. The first half of this review discusses new discoveries in the pathogenesis of acne, and the second half introduces new and time-honored therapies.

Acne Vulgaris↗

PubMed2003

Dock and Pak regulate olfactory axon pathfinding in Drosophila.

The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses.

One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Transfection of TLR2 into a nonresponsive cell line was sufficient for NF-kappa B activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout, and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes. P. acnes also induced activation of IL-12 p40 promoter activity via TLR2. Furthermore, P. acnes induced IL-12 and IL-8 protein production by primary human monocytes and this cytokine production was inhibited by anti-TLR2 blocking Ab. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for treatment of this common skin disease.

Acne Vulgaris↗