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Rosdahl, Inger
Publications (10 of 63) Show all publications
Wäster, P., Eriksson, I., Vainikka, L., Rosdahl, I. & Öllinger, K. (2016). Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation. Scientific Reports, 6(27890)
Open this publication in new window or tab >>Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 27890Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-130287 (URN)10.1038/srep27890 (DOI)000378036300001 ()27293048 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; Welander-Finsen Foundation; County Council of Ostergotland; Stiftelsen Olle Engkvist Byggmastare; Konung Gustav V och Drottning Victorias Frimurarestiftelse; Ostgotaregionens Cancerfond

Available from: 2016-08-01 Created: 2016-07-28 Last updated: 2017-11-28
Shrestha, D., Baral, S., Shrestha, R., Gupta, S., Bhattarai, S., Shrestha, S. & Rosdahl, I. (2015). Frequency and pattern of Skin Disorders in Adolescentsin a School of Kathmandu. Journal of Institute of Medicine, 37(1), 21-25
Open this publication in new window or tab >>Frequency and pattern of Skin Disorders in Adolescentsin a School of Kathmandu
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2015 (English)In: Journal of Institute of Medicine, ISSN 1993-2979, Vol. 37, no 1, p. 21-25Article in journal (Refereed) Published
Abstract [en]

Skin disorders are one of the major causes of morbidity in Nepal. The objectives of this study are to determine the relative frequency and pattern of skin disordersin a cohort of adolescents 9-18 years of age.

Methods: The study was conducted in a residential school of Kathmandu. A detailedinformation about the study was given to the student members of a school club and they inturn, informed all the other students of the dermatologic health camp, which was conductedsubsequently. All students appearing at the camp were examined by a dermatologist andinformation regarding age, gender, school grade and diagnosis were recorded in a prevalidatedformat.

Results: In the school there were a total of 950 students (627 m, 323 f). Of them 242 (116 m,126 f) had skin disorder with a point prevalence of 25.5%. Female students had significantlyhigher prevalence (29%) than male (18.5%). The most common skin disorders were acne,eczemas and urticaria, and the 10 most frequent diagnoses comprised 87% of all skinconditions.Conclusion: This study demonstrates that 1/4 of the students had one or more identifiableskin disorders. Despite the wide range of dermatoses, only a few of them accounted for amajor proportion of the skin disorders. This study provides data for targeting health careprograms for prevention and treatment of skin disorders in this age group.

Keywords
Skin disorders, adolescents, frequency, pattern
National Category
Dermatology and Venereal Diseases Psychiatry
Identifiers
urn:nbn:se:liu:diva-120543 (URN)
Available from: 2015-08-14 Created: 2015-08-14 Last updated: 2015-09-11Bibliographically approved
Bivik Eding, C., Domer, J., Wäster, P., Jerhammar, F., Rosdahl, I. & Öllinger, K. (2015). Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases. Acta Dermato-Venereologica, 95(7), 792-797
Open this publication in new window or tab >>Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases
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2015 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

Place, publisher, year, edition, pages
ACTA DERMATO-VENEREOLOGICA, 2015
Keywords
lysosome; cathepsin; UVA; exocytosis; melanocyte; melanoma
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-122545 (URN)10.2340/00015555-2064 (DOI)000362925500005 ()25669167 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Ostgotaregionens Cancer Foundation; Stiftelsen Olle Engkvist Byggmastare; Swedish Cancer Society; Welander-Finsen Foundation

Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2017-12-01
Wäster, P., Rosdahl, I. & Öllinger, K. (2014). Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.. British Journal of Dermatology, 171(6), 1336-1346
Open this publication in new window or tab >>Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.
2014 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1336-1346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.

OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.

METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.

RESULTS: UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.

CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112883 (URN)10.1111/bjd.13278 (DOI)000347236100174 ()25046326 (PubMedID)
Note

Funding text:

This study was supported by the Swedish Research Council, the Swedish Cancer Society, the County Council of Ostergotland, Konung Gustav V och Drottning Victorias Frimurarestiftelse and the Welander-Finsen Foundation.

Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2018-01-11Bibliographically approved
Thunell, L., Bivik, C., Wäster, P., Fredrikson, M., Stjernstrom, A., Synnerstad, I., . . . Enerbäck, C. (2014). MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma. Melanoma research, 24(3), 190-197
Open this publication in new window or tab >>MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma
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2014 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 24, no 3, p. 190-197Article in journal (Refereed) Published
Abstract [en]

The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 pathway in 258 individuals with sporadic malignant melanomas, 50 with hereditary malignant melanomas, and 799 healthy controls. Genotyping was performed by PCR-restriction fragment length polymorphism, pyrosequencing, and allelic discrimination. We found an increased risk for hereditary melanoma in MDM2 GG homozygotes, which was more pronounced among women (P=0.035). In the event of pairwise combinations of the single nucleotide polymorphisms, a risk elevation was shown for MDM2 GG homozygotes/p53 wild-type Arg in hereditary melanoma (P=0.01). Individuals with sporadic melanomas of the superficial spreading type, including melanoma in situ, showed a slightly higher frequency of the MDM2 GG genotype compared with those with nodular melanomas (P=0.04). The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005). In conclusion, the results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women. Analysis of sporadic melanoma also shows an association between MDM2 and the superficial spreading melanoma subtype, as well as an association with the presence of dysplastic nevi in sporadic melanoma.

Place, publisher, year, edition, pages
Lippincott, Williams andamp; Wilkins, 2014
Keywords
superficial spreading melanoma; MDM2; hereditary melanoma; MDM4; p53; dysplastic nevi
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107446 (URN)10.1097/CMR.0000000000000063 (DOI)000335683500002 ()
Available from: 2014-06-12 Created: 2014-06-12 Last updated: 2017-12-05
Shrestha, R., Shrestha, D., Lama, L., Gurung, D. & Rosdahl, I. (2014). Pattern Of Skin Diseases In A Rural Village Development Community Of Nepal. Nepal Journal of Dermatology, Venereology & Leprology, 12(1), 41-44
Open this publication in new window or tab >>Pattern Of Skin Diseases In A Rural Village Development Community Of Nepal
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2014 (English)In: Nepal Journal of Dermatology, Venereology & Leprology, ISSN 2091-167X, Vol. 12, no 1, p. 41-44Article in journal (Refereed) Published
Abstract [en]

Introduction: Skin diseases are a common cause of morbidity in Nepal as per the health services report. There is limited information on the prevalence and pattern of skin diseases in the community. The objective of this study was to determine the pattern of skin diseases in a rural village development community of Nepal.

Materials and methods:  Two  dermatologic  health camps were conducted, during which, the villagers were examined by dermatologists. The skin diseases diagnosed were recorded in a proforma.

Results: There were 433 individuals examined and 359 (male-47.9%; female-52.1%) had skin disease identified clinically (camp prevalence- 83%). The age of patients ranged from 1 to 80 years (mean-24.5; SD±15.9), with majority in the age group of 10-19 years. The most common skin disease category was eczemas (36.4%), followed by infections (28.4%), acne (22%), pigment disorders (34%) and urticaria (12.3%).

Conclusion: Skin diseases were common in the community. The five most common Skin disease categories were eczemas, infections, acne and pigment disorders were the more common conditions.

Place, publisher, year, edition, pages
Kathmandu, Nepal: Nepal Journals OnLine, 2014
Keywords
Acne; eczema; infection; pattern of skin diseases; pigment disorder; village development community
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110309 (URN)10.3126/njdvl.v12i1.10595 (DOI)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2015-05-06Bibliographically approved
Shrestha, D., Gurung, D., Shrestha, R. & Rosdahl, I. (2014). Skin Diseases and Impact on Quality of Life in the Central Development Region of Nepal: A major public health problem. Journal of Institute of Medicine, 36(2), 15-20
Open this publication in new window or tab >>Skin Diseases and Impact on Quality of Life in the Central Development Region of Nepal: A major public health problem
2014 (English)In: Journal of Institute of Medicine, ISSN 1993-2979, Vol. 36, no 2, p. 15-20Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Kathmandu, Nepal: , 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110307 (URN)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2014-10-14Bibliographically approved
Shrestha, D. P., Shrestha, R., Gurung, D., Lama, L. & Rosdahl, I. (2013). Development of skin disease disability index to assess the dermatologic burden in Nepal. Institute of Medicine. Journal, 35(2), 24-29
Open this publication in new window or tab >>Development of skin disease disability index to assess the dermatologic burden in Nepal
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2013 (English)In: Institute of Medicine. Journal, ISSN 1993-2979, Vol. 35, no 2, p. 24-29Article in journal (Refereed) Published
Abstract [en]

Introduction: Skin disease is one of the leading cause of morbidity worldwide. Most instruments measuring the impact of skin disease on quality of life are developed in the west and not applicable to the socio-cultural situation in Nepal. The aim of the study was to develop and validate a questionnaire to measure quality of life impairment due to skin disease in Nepal.

Methods: Different aspects of quality of life impairment were identiÞ ed from 35 in-depth interviews and two focus group discussions, with villagers with various skin diseases. Based on this information, 10 questions scoring the influence of skin diseases on quality of life – Skin Disease Disability Index (SDDI) – was developed. This instrument was tested and validated in 212 villagers with skin disease and in 100 healthy villagers.

Results: The maximum total Skin Disease Disability Index score was 36. There was a wide variation in total Skin Disease Disability Index score between individuals with skin disease (range 1-33) with a mean score of 13.2, while in controls the mean total score was 1 (p<0.001). Thus, the Skin Disease Disability Index clearly discriminates between these two groups. The difference in mean score for single questions between patients and controls was also highly significant (p<0.001).

Conclusions: The questionnaire clearly covered all aspects of quality of life related to skin disease and was, simple, robust, easy to use and well accepted by the selected population. The Skin Disease Disability Index was reliable in the overall score as well as in individual questions.

Place, publisher, year, edition, pages
Kathmandu, Nepal: Institute of Medicine, 2013
Keywords
Skin disease; Disability index; Health burden; Nepal
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-101087 (URN)
Available from: 2013-11-19 Created: 2013-11-19 Last updated: 2015-11-17
Bivik, C., Verma, D., Winge, M. C., Lieden, A., Bradley, M., Rosdahl, I. & Söderkvist, P. (2013). Letter: Genetic Variation in the Inflammasome and Atopic Dermatitis Susceptibility [Letter to the editor]. Journal of Investigative Dermatology, 133(10), 2486-2489
Open this publication in new window or tab >>Letter: Genetic Variation in the Inflammasome and Atopic Dermatitis Susceptibility
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2013 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 133, no 10, p. 2486-2489Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Hybrid Model Option A, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-99395 (URN)10.1038/jid.2013.168 (DOI)000324899100028 ()
Available from: 2013-10-17 Created: 2013-10-17 Last updated: 2017-12-06
Appelqvist, H., Wäster, P., Eriksson, I., Rosdahl, I. & Öllinger, K. (2013). Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes. Journal of Cell Science, 126(24), 5578-5584
Open this publication in new window or tab >>Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes
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2013 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 126, no 24, p. 5578-5584Article in journal (Refereed) Published
Abstract [en]

Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the development of skin cancer. To elucidate the initial signaling during UV-induced damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis induction. UVA, but not UVB, induced plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two hours after UVA irradiation, we detected activation of caspase-8, which was reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and apoptosis was reduced by prevention of endocytosis and by the use of cathepsin inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte response to UVA and is followed by cathepsin-dependent activation of caspase-8. The findings have implications for the understanding of UV-induced skin damage and emphasize that UVA and UVB initiate apoptosis through different signaling pathways in keratinocytes.

Place, publisher, year, edition, pages
Company of Biologists, 2013
Keywords
Keratinocyte; UV irradiation; Lysosome; Cathepsin; Endocytosis; Apoptosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103290 (URN)10.1242/jcs.130633 (DOI)000328686600005 ()
Note

The previous status of this article was manuscript with the title Lysosomal exocytosis repairs the plasma membrane after UVA and is followed by caspase-8 induced apoptosis.

Available from: 2014-01-17 Created: 2014-01-16 Last updated: 2017-08-30
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