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Ihnatko, Robert, PhDORCID iD iconorcid.org/0000-0001-5751-3622
Publications (10 of 15) Show all publications
Matsuwaki, T., Shionoya, K., Ihnatko, R., Eskilsson, A., Kakuta, S., Dufour, S., . . . Blomqvist, A. (2017). Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses. Brain, behavior, and immunity, 66, 165-176
Open this publication in new window or tab >>Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses
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2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 66, p. 165-176Article in journal (Refereed) Published
Abstract [en]

Sickness responses to lipopolysaccharide (LPS) were examined in mice with deletion of the interleukin (IL)-1 type 1 receptor (IL-1R1). IL-1R1 knockout (1(0) mice displayed intact anorexia and HPA-axis activation to intraperitoneally injected LPS (anorexia: 10 or 120 mu g/kg; HPA-axis: 120 mu g/kg), but showed attenuated but not extinguished fever (120 g/kg). Brain PGE2 synthesis was attenuated, but Cox-2 induction remained intact. Neither the tumor necrosis factor-alpha (TNF alpha) inhibitor etanercept nor the IL -6 receptor antibody tocilizumab abolished the LPS induced fever in IL -1R1 KO mice. Deletion of IL -1R1 specifically in brain endothelial cells attenuated the LPS induced fever, but only during the late, 3rd phase of fever, whereas deletion of IL-1R1 on neural cells or on peripheral nerves had little or no effect on the febrile response. We conclude that while IL-1 signaling is not critical for LPS induced anorexia or stress hormone release, IL-1R1, expressed on brain endothelial cells, contributes to the febrile response to LPS. However, also in the absence of IL-1R1, LPS evokes a febrile response, although this is attenuated. This remaining fever seems not to be mediated by IL-6 receptors or TNFa, but by some yet unidentified pyrogenic factor. 

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Interleukin-1 type 1 receptor; Lipopolysaccharide; Fever; Anorexia; ACTH; Corticosterone; Endothelial cells; THF alpha; Interleukin-6; PGE(2)
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-143084 (URN)10.1016/j.bbi.2017.06.013 (DOI)000414236600018 ()28655587 (PubMedID)
Note

Funding Agencies|Japan Society for the Promotion of Science [15K18800]; Swedish Research Council [20725, 07879]; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland; Sixth Research Framework Programme of the European Union, Project MUGEN [MUGEN LSHG-CT-2005-005203]; MRC research grant [G0801296]

Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2018-06-18
Ihnatko, R. & Theodorsson, E. (2017). Short N-terminal galanin fragments are occurring naturally in vivo. Neuropeptides, 63
Open this publication in new window or tab >>Short N-terminal galanin fragments are occurring naturally in vivo
2017 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 63Article in journal (Refereed) Published
Abstract [en]

The galanin family currently consists of four peptides, namely galanin, galanin-message associated peptide, galanin-like peptide and alarin. Unlike galanin that signals through three different G protein-coupled receptors; GALL, GAL(2), and GAL(3), binding at its N-terminal end, the cognate receptors for other members of the galanin family are currently unknown. Research using short N-terminal galanin fragments generated either by enzymatic cleavage or solid-phase synthesis has revealed differences in their receptor binding properties exerting numerous biological effects distinct from galanin(1-29) itself. Our studies on tissue extracts derived from rat small intestine and bovine gut using chromatographic techniques and sensitive galanin(1-16)-specific radioimmunoassay revealed the presence of immunoreactive compounds reacting with antiserum against galanin(1-16) distributed in distinct elution volumes. These results suggested a possible presence of short N-terminal galanin fragments also in vivo. Moreover, employing immunoaffinity chromatography and reverse-phase high performance liquid chromatography (HPLC) followed by mass spectrometry allowed specific enrichment of these immunoreactive compounds from rat tissues and identification of their molecular structure. Indeed, our study revealed presence of several distinct short N-terminal galanin sequences in rat tissue. To prove their receptor binding, four of the identified sequences were synthetized, namely, galanin(1-13), galanin(1-16), galanin(1.20), galanin(6-20), and tested on coronal rat brain sections competing with I-125-labeled galanin(1-29). Our autoradiographs confirmed that galanin(1-13), galanin(1-16), and galanin(1-20) comprehensively displaced I-125-galanin(1-29) but galanin (6-20) did not. Here we show, for the first time, that short N-terminal galanin fragments occur naturally in rat tissues and that similar or identical galanin sequences can be present also in tissues of other species. Biological significance: This study is first to provide an evidence of the presence of short N-terminal galanin fragments in vivo in a biological system and provides further foundations for the previous studies using synthetized short N-terminal galanin fragments.

Place, publisher, year, edition, pages
Churchill Livingstone, 2017
Keywords
Galanin; Receptor; Neuropeptide; Affinity chromatography; High-performance liquid chromatography (HPLC); Mass spectrometry (MS); Post-translational modification (PTM); Autoradiography
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-139625 (URN)10.1016/j.npep.2017.03.005 (DOI)000405880200001 ()28434790 (PubMedID)2-s2.0-85018571577 (Scopus ID)
Note

Funding Agencies|County Council of Ostergotland

Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2017-09-08Bibliographically approved
Ihnatko, R., Edén, U., Fagerholm, P. & Lagali, N. (2016). Congenital Aniridia and the Ocular Surface. OCULAR SURFACE, 14(2), 196-206
Open this publication in new window or tab >>Congenital Aniridia and the Ocular Surface
2016 (English)In: OCULAR SURFACE, ISSN 1542-0124, Vol. 14, no 2, p. 196-206Article in journal (Refereed) Published
Abstract [en]

Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye structures, including the cornea, iris, anterior chamber angle, lens, and fovea. The ocular surface, in particular, can be severely affected by a progressive pathology termed aniridia-associated keratopathy (AAK), markedly contributing to impaired vision. The purpose of this review is to provide an update of the current knowledge of the genetic, clinical, micro-morphological, and molecular aspects of AAK. We draw upon material presented in the literature and from our own observations in large aniridia cohorts. We summarize signs and symptoms of AAK, describe current options for management, and discuss the latest research findings that may lead to better diagnosis and new treatment or prevention strategies for this debilitating ocular surface condition.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2016
Keywords
aniridia; aniridia-associated keratopathy; congenital aniridia; gene mutations; haplo-insufficiency; iris; Pax6 gene
National Category
Psychiatry
Identifiers
urn:nbn:se:liu:diva-128758 (URN)10.1016/j.jtos.2015.10.003 (DOI)000375222400012 ()
Note

Funding Agencies|Ogonfonden; Swedish Research Council [2012-2472]; Country of Ostergotland; Kronprinsessan Margaretas Arbetsnamnd

Available from: 2016-05-31 Created: 2016-05-30 Last updated: 2018-01-22
Ihnatko, R., Edén, U., Lagali, N., Dellby, A. & Fagerholm, P. (2013). Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia. Journal of Proteomics, 94, 78-88
Open this publication in new window or tab >>Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia
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2013 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 94, p. 78-88Article in journal (Refereed) Published
Abstract [en]

Aniridia is a rare congenital genetic disorder caused by haploinsuffiency of the PAX6 gene, the master gene for development of the eye. The expression of tear proteins in aniridia is unknown. To screen for proteins involved in the aniridia pathophysiology, the tear fluid of patients with diagnosed congenital aniridia was examined using two-dimensional electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two-dimensional map of tear proteins in aniridia has been established and 7 proteins were differentially expressed with P less than 0.01 between aniridia patients and control subjects. Five of them were more abundant in healthy subjects, particularly alpha-enolase, peroxiredoxin 6, cystatin S, gelsolin, apolipoprotein A-1 and two other proteins, zinc-alpha 2-glycoprotein and lactoferrin were more expressed in the tears of aniridia patients. Moreover, immunoblot analysis revealed elevated levels of vascular endothelial growth factor (VEGF) in aniridia tears which is in concordance with clinical finding of pathological blood and lymph vessels in the central and peripheral cornea of aniridia patients. The proteins with different expression in patients tears may be new candidate molecules involved in the pathophysiology of aniridia and thus may be helpful for development of novel treatment strategies for the symptomatic therapy of this vision threatening condition. Biological significance This study is first to demonstrate protein composition and protein expression in aniridic tears and identifies proteins with different abundance in tear fluid from patients with congenital aniridia vs. healthy tears.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Aniridia; Keratopathy; Tear fluid; Two-dimensional electrophoresis; LC-MS/MS; alpha-Enolase
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-104841 (URN)10.1016/j.jprot.2013.09.003 (DOI)000330493400006 ()
Available from: 2014-02-28 Created: 2014-02-28 Last updated: 2018-01-22
Ihnatko, R., Post, C. & Blomqvist, A. (2013). Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia. British Journal of Cancer, 109(7), 1867-1875
Open this publication in new window or tab >>Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia
2013 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 109, no 7, p. 1867-1875Article in journal (Refereed) Published
Abstract [en]

Background:

Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain’s metabolic control centre.

Methods:

The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry.

Results:

The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia.

Conclusion:

The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

Place, publisher, year, edition, pages
Cancer Research UK, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-100305 (URN)10.1038/bjc.2013.525 (DOI)000325216700021 ()
Note

Funding Agencies|Swedish Cancer Foundation|12 0553|Swedish Research Council|12X-07879|

Available from: 2013-11-04 Created: 2013-11-04 Last updated: 2019-02-11Bibliographically approved
Ihnatko, R., Shaw, E. & Toman, R. (2012). Proteome of Coxiella burnetii. In: Rudolf Toman, Robert A. Heinzen, James E. Samuel and Jean-Louis Mege (Ed.), Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium (pp. 105-130). Springer-Verlag New York, 984
Open this publication in new window or tab >>Proteome of Coxiella burnetii
2012 (English)In: Coxiella burnetii: Recent Advances and New Perspectives in Research of the Q Fever Bacterium / [ed] Rudolf Toman, Robert A. Heinzen, James E. Samuel and Jean-Louis Mege, Springer-Verlag New York, 2012, Vol. 984, p. 105-130Chapter in book (Refereed)
Abstract [en]

Recent proteomic studies of C. burnetii, the etiological agent of Q fever, have brought a deeper insight into the pathogens physiology and offered new possibilities in investigations of inter- or intra-species relatedness. The data generated from these studies in conjunction with the current genomic sequence databases may reveal additional identities for conserved and unique C. burnetii biomarkers and aid in creating algorithms and/or databases that could develop into diagnostic and detection tools for the pathogen. Moreover, wide scale screening and further characterization of potential C. burnetii protein antigens along with a comprehensive evaluation of the humoral immune response will be of fundamental importance towards research and development of a safe and efficacious vaccine as well as improved serodiagnostic tests for rapid and sensitive detection of the Q fever pathogen. Given these advances, proteomics may make marked contributions to the improvement of human health protection against C. burnetii in the coming years.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2012
Series
Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019 ; 984
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-80251 (URN)10.1007/978-94-007-4315-1_6 (DOI)000333215000007 ()22711629 (PubMedID)9789400743144 (ISBN)9789400743151 (ISBN)9789400792050 (ISBN)
Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2018-03-05Bibliographically approved
Vadovič, P., Ihnatko, R. & Toman, R. (2011). Composition and Structure of Lipid A of the Intracellular Bacteria Piscirickettsia Salmonis and Coxiella Burnetii. In: Jiri Stulik, Rudolf Toman, Patrick Butaye and Robert G. Ulrich (Ed.), BSL3 and BSL4 Agents: Proteomics, Glycomics, and Antigenicity (pp. 139-144). Wiley-VCH Verlag GmbH & Co. KGaA
Open this publication in new window or tab >>Composition and Structure of Lipid A of the Intracellular Bacteria Piscirickettsia Salmonis and Coxiella Burnetii
2011 (English)In: BSL3 and BSL4 Agents: Proteomics, Glycomics, and Antigenicity / [ed] Jiri Stulik, Rudolf Toman, Patrick Butaye and Robert G. Ulrich, Wiley-VCH Verlag GmbH & Co. KGaA , 2011, p. 139-144Chapter in book (Refereed)
Place, publisher, year, edition, pages
Wiley-VCH Verlag GmbH & Co. KGaA, 2011
Keywords
lipid A, Piscirickettsia salmonis, Coxiella burnetii, chemical composition, structure, endotoxic activity
National Category
Immunology Biomedical Laboratory Science/Technology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-145521 (URN)10.1002/9783527638192.ch13 (DOI)9783527327805 (ISBN)9783527638192 (ISBN)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-03-09Bibliographically approved
Ihnatko, R., Vadovič, P. & Toman, R. (2011). Proteins of Coxiella Burnetii and Analysis of their Function. In: Jiri Stulik, Rudolf Toman, Patrick Butaye and Robert G. Ulrich (Ed.), BSL3 and BSL4 Agents: Proteomics, Glycomics, and Antigenicity (pp. 145-151). Wiley-VCH Verlag GmbH & Co. KGaA
Open this publication in new window or tab >>Proteins of Coxiella Burnetii and Analysis of their Function
2011 (English)In: BSL3 and BSL4 Agents: Proteomics, Glycomics, and Antigenicity / [ed] Jiri Stulik, Rudolf Toman, Patrick Butaye and Robert G. Ulrich, Wiley-VCH Verlag GmbH & Co. KGaA , 2011, p. 145-151Chapter in book (Refereed)
Place, publisher, year, edition, pages
Wiley-VCH Verlag GmbH & Co. KGaA, 2011
Keywords
Coxiella burnetii, proteins, function, proteomics
National Category
Immunology in the medical area Microbiology in the medical area Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-145522 (URN)10.1002/9783527638192.ch14 (DOI)9783527327805 (ISBN)9783527638192 (ISBN)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-03-05Bibliographically approved
Palkovicova, K., Ihnatko, R., Vadovic, P., Betinova, E., Skultety, L., Frangoulidis, D. & Toman, R. (2009). A monoclonal antibody specific for a unique biomarker, virenose, in a lipopolysaccharide of Coxiella burnetii. Clinical Microbiology and Infection, 15 Suppl 2, 183-4
Open this publication in new window or tab >>A monoclonal antibody specific for a unique biomarker, virenose, in a lipopolysaccharide of Coxiella burnetii
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2009 (English)In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15 Suppl 2, p. 183-4Article in journal (Refereed) Published
Abstract [en]

Q fever is a zoonotic disease caused by Coxiella burnetii. Easy aerosol dissemination, strong environmental persistence and high infectivity make the bacterium a serious threat for humans and animals. A rapid, sensitive and specific test for the infectious agent is still a challenge in the field. C. burnetii expresses a spectrum of amphophilic macromolecules on its surface. Among them, a lipopolysaccharide (LPS) is of particular biological, immunological and medical significance [1]. Upon serial laboratory passages in yolk sacs of embryonated hen eggs, C.

Place, publisher, year, edition, pages
Elsevier, 2009
National Category
Microbiology in the medical area Infectious Medicine Pharmacology and Toxicology Immunology in the medical area Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-145507 (URN)10.1111/j.1469-0691.2008.02218.x (DOI)000272864900085 ()19438626 (PubMedID)
Available from: 2018-03-03 Created: 2018-03-03 Last updated: 2019-01-22Bibliographically approved
Toman, R., Skultety, L. & Ihnatko, R. (2009). Coxiella burnetii glycomics and proteomics--tools for linking structure to function. Annals of the New York Academy of Sciences, 1166, 67-78
Open this publication in new window or tab >>Coxiella burnetii glycomics and proteomics--tools for linking structure to function
2009 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1166, p. 67-78Article in journal (Refereed) Published
Abstract [en]

Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular bacterium and a highly infectious pathogen. The disease is a widespread zoonosis and is endemic throughout the world. An easy aerosol dissemination, environmental persistence, and high infectivity make the bacterium a serious threat for humans and animals. Lipopolysaccharide is considered one of the major factors of virulence expression and infection of the bacterium. Detailed glycomic studies enabled to better understand structural and functional peculiarities of this biopolymer and its role in pathogenesis and immunity of Q fever. Recent proteomic studies of C. burnetii have brought new approaches in accurate detection of the infectious agent and offered new insights into the inter- or intra-species relatedness. Thus, structure/function relationship studies are currently of utmost importance in the field. This paper will focus on glycomic and proteomic approaches providing information on unique glycan and protein species of the microorganism as the candidate molecules for the use in detection/diagnosis, therapy, and prophylaxis.

Place, publisher, year, edition, pages
John Wiley & Sons, 2009
National Category
Microbiology in the medical area Infectious Medicine Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-145506 (URN)10.1111/j.1749-6632.2009.04512.x (DOI)000267264400007 ()19538265 (PubMedID)
Available from: 2018-03-03 Created: 2018-03-03 Last updated: 2019-01-22Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-5751-3622

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