Date: Monday, November 9, 2015
Session Title: Systemic Lupus Erythematosus - Animal Models Poster I
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Excessive exposure to sunlight, particularly ultraviolet B (UVB), induces autoimmune skin inflammation and other skin diseases. Although UVB mainly causes damage to the epidermis, photodamage is followed by inflammatory responses, which can be highly detrimental. Skin inflammation in turn can further exacerbate photodamage and, if recurring or long-lasting, can induce pathogenic alterations. Previous studies from ours and other groups showed that the immediate response in the skin to UVB exposure is to induce the release of TNFα and other inflammatory cytokines from keratinocytes in the epidermis. Neutrophils are the most common circulating leukocyte. Similar to other injury or acute inflammation, neutrophils are also the earliest immune cells recruited to the site of photodamage in response to UVB exposure, followed by the monocyte/macrophages and T lymphocytes. However, little is known about the role of neutrophils in UVB-induced skin inflammation, and previous photobiology studies have mainly focused on the role of other cell types on UVB-induced detrimental effects in skin. Neutrophil NETosis, a novel type of neutrophil cell death, releases neutrophil extracellular traps (NETs) that have been shown to be important in autoimmune inflammation. Given that the induction of TNFα and infiltration of neutrophils both appear within hours after UVB exposure, and neutrophils are unable to become NETotic in TNFα KO mice, we sought to determine whether UVB exposure can induce neutrophil NETosis in vivo.
Human primary neutrophils were treated without or with TNFα to study the in vitro effects of TNFα on neutrophil NETosis. To explore the effects of UVB exposure on neutrophil NETosis in vivo during the skin inflammatory responses, we exposed C57/BL6 wild-type and MRL/lpr lupus prone mice to UVB according to our published protocol with minor modification.
In the in vitro study, we found the increased neutrophil NETosis when we treated human primary neutrophils with TNFα, a proinflammatory cytokine that can be induced in UVB-exposed mice. In the in vivo study, our preliminary experiments showed that UVB exposure (250 mJ/cm2/day for 5 consecutive days) of female wild-type mice significantly induces skin inflammation with infiltration of inflammatory cells, and many of the infiltrated neutrophils become NETotic in the inflamed skin of the UVB exposed WT mice as compared to sham WT mice without UVB exposure. Similarly, we found that UVB exposure (100 mJ/cm2/day for 10 consecutive days) can also induce neutrophil NETosis in UVB-irradiated MRL/lpr lupus-prone mice
Our studies indicate that UVB exposure of mice can induce skin inflammation with increased neutrophil NETosis, possibly through the induction of the proinflammatory cytokine, TNFα. Neutrophil NETosis may be involved in UVB-induced skin inflammation.
To cite this abstract in AMA style:Liu ML, Sharma M, Sahu S, Werth V. Neutrophil Netosis Formation during the UVB Induced-Skin Inflammation [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/neutrophil-netosis-formation-during-the-uvb-induced-skin-inflammation/. Accessed May 13, 2021.
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