Urocanic acid suppresses the activation of human neutrophils in vitro

K, Kivistö; Punnonen, Kari; Toppari, Jorma; Leino, Lasse

doi:10.1007/bf01487038

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…There are several potential candidates, of which urocanic acid and cytokines are the most likely ones. We have recently shown that urocanic acid, which has been implicated as the photoreceptor within the skin for UV radiation and mediator of some immune suppressive effects of UVB, is not able to down-modulate CR expression in human neutrophils in vitro [36]. It is well established that UVB-irradiated keratinocytes secrete a wide variety of modulatory cytokines, of which tumor necrosis factor ␣ and interleukin-10 are perhaps the most important [37,38].…”

Section: Discussionmentioning

confidence: 99%

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Leino

Saarinen

et al. 1999

Journal of Leukocyte Biology

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We examined systemic effects of wholebody UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5-and 24-h time points, respectively. The down-modulation of CRs after whole-body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM-1 was detected after UVB, which rules out CD11b epitope masking by sICAM-1. UVB did not release low-receptor-density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB-induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole-body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down-modulation of preexisting cell-surface receptors, suppress some important functions of circulating phagocytic cells. J. Leukoc. Biol. 65: 573-582; 1999.

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Section: Discussionmentioning

confidence: 99%

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Leino

Saarinen

et al. 1999

Journal of Leukocyte Biology

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“…The cis-UCA, formed from trans-UCA upon UV-B exposure, has been implicated in the down-regulation of hypersensitivity reactions [2,3] in the actions of epidermal antigen-presenting cells [4,5], the activation of neutrophils [6,7], and the prolonged survival of organ transplants [8], but the mechanisms of action still remain to be resolved.…”

Section: Introductionmentioning

confidence: 99%

Cis‐urocanic acid suppresses UV‐B‐induced interleukin‐6 secretion and cytotoxicity in human corneal and conjunctival epithelial cells in vitro

Viiri

Jauhonen

Ryhänen

et al. 2009

Acta Ophthalmologica

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PurposeUrocanic acid (UCA) is a major ultraviolet (UV)-absorbing endogenous chromophore in the epidermis and is also an efficacious immunosuppressant. The anti-inflammatory and cytoprotective effects of cis-UCA were studied in ocular surface cell cultures exposed to UV-B irradiation. MethodsHuman corneal epithelial cells (HCE-2) and human conjunctival epithelial cells (HCECs) were incubated with 10, 100, 1,000, and 5,000 μg/ml cis-UCA with and without a single UV-B irradiation dose. The concentrations of IL-1β, IL-6, IL-8, and TNF-α in the culture medium and caspase-3 activity in the cell extract sampled were measured by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured by the colorimetric MTT (3-(4,5-dimethyldiazol- 2-yl)-2,5-diphenyltetrazolium bromide) assay. ResultsUV-B irradiation multiplied interleukin IL-6 and IL-8 secretion levels in HCE-2 cells and HCECs as analyzed with ELISA. Cell viability as measured by the MTT assay declined by 30%–50% in HCE-2 cells and by 20%–40% in HCECs after UV-B irradiation. Moreover, UV-B increased caspase-3 activity in both cell types as analyzed with ELISA. Treatment with 100 μg/ml cis-UCA completely suppressed IL-6 and IL-8 secretion, decreased caspase-3 activity, and improved cell viability against UV-B irradiation. No significant effects on IL-6 or IL-8 secretion, caspase-3 activity, or viability of the non-irradiated cells were observed with 100 μg/ml cis-UCA in both cell types. The 5,000 μg/ml concentration was toxic. ConclusionsThese findings indicate that cis-UCA may represent a promising anti-inflammatory and cytoprotective treatment option to suppress UV-B-induced inflammation and cellular damage in human corneal and conjunctival epithelial cells.

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“…In contrast to our finding, Rinaldi et al (2006) have shown that cis-UCA inhibits the generation of extracellular superoxide while not affecting the generation of intracellular superoxide or other ROS in bovine neutrophils. Although they did not test trans-UCA, this inhibitory effect is unlikely to be specific to the cis-isomer because it has previously been shown that either trans-or cis-UCA inhibits the respiratory burst activity of human neutrophils (Kivisto et al, 1996). UCA is an imidazole compound and, as well as other imidazole derivatives including histidine and histamine, both UCA isomers are known to act as hydroxyl radical scavengers in aqueous solution (Kammeyer et al, 1999).…”

Section: Discussionmentioning

confidence: 97%

cis-Urocanic Acid Enhances Prostaglandin E2 Release and Apoptotic Cell Death via Reactive Oxygen Species in Human Keratinocytes

Kaneko

Walker

Lai-Cheong

et al. 2011

Journal of Investigative Dermatology

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Urocanic acid (UCA) is a major UVR-absorbing skin molecule that undergoes trans to cis photoisomerization in the epidermis following UVR exposure. Murine studies have established that cis-UCA is an important mediator of UVR-induced immune suppression, but little is known about its signaling pathway. We have previously demonstrated that treatment of normal human epidermal keratinocytes with cis-UCA resulted in increased synthesis of prostaglandin E(2) (PGE(2)) and cell death. Here, using immortalized human keratinocytes, we report that cis-UCA but not trans-UCA generates reactive oxygen species (ROS) in a dose-dependent manner and that the natural antioxidant α-tocopherol can reduce this ROS generation, subsequent PGE(2) release, and apoptotic cell death. Western blot analysis revealed that cis-UCA leads to a transient phosphorylation of EGFR as well as downstream mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and p38. Pharmacological inhibition of their activity attenuated PGE(2) release induced by cis-UCA. After transient activation, cis-UCA downregulated EGFR protein expression that corresponded to activation of caspase-3. In addition, pretreatment with α-tocopherol inhibited EGFR downregulation and caspase-3 activation induced by cis-UCA. These results suggest that cis-UCA exerts its effects on human keratinocytes via intracellular ROS generation that modulates EGFR signaling and subsequently induces PGE(2) synthesis and apoptotic cell death.

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Urocanic acid suppresses the activation of human neutrophils in vitro

Cited by 14 publications

References 23 publications

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation

Cis‐urocanic acid suppresses UV‐B‐induced interleukin‐6 secretion and cytotoxicity in human corneal and conjunctival epithelial cells in vitro

cis-Urocanic Acid Enhances Prostaglandin E2 Release and Apoptotic Cell Death via Reactive Oxygen Species in Human Keratinocytes

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