scholarly journals Chemokine Signatures in the Skin Disorders of Lyme Borreliosis in Europe: Predominance of CXCL9 and CXCL10 in Erythema Migrans and Acrodermatitis and CXCL13 in Lymphocytoma

2007 ◽  
Vol 75 (9) ◽  
pp. 4621-4628 ◽  
Author(s):  
Robert R. Müllegger ◽  
Terry K. Means ◽  
Junghee J. Shin ◽  
Marshall Lee ◽  
Kathryn L. Jones ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mrna Expression ◽  
Lyme Borreliosis ◽  
Erythema Migrans ◽  
Mrna Levels ◽  
Skin Disorders ◽  
Lesional Skin ◽  
Acrodermatitis Chronica Atrophicans ◽  
Reverse Transcription Pcr

ABSTRACT The three skin disorders of Lyme borreliosis in Europe include erythema migrans, an acute, self-limited lesion; borrelial lymphocytoma, a subacute lesion; and acrodermatitis chronica atrophicans, a chronic lesion. Using quantitative reverse transcription-PCR, we determined mRNA expression of selected chemokines, cytokines, and leukocyte markers in skin samples from 100 patients with erythema migrans, borrelial lymphocytoma, or acrodermatitis chronica atrophicans and from 25 control subjects. Chemokine patterns in lesional skin in each of the three skin disorders included low but significant mRNA levels of the neutrophil chemoattractant CXCL1 and the dendritic cell chemoattractant CCL20 and intermediate levels of the macrophage chemoattractant CCL2. Erythema migrans and particularly acrodermatitis lesions had high mRNA expression of the T-cell-active chemokines CXCL9 and CXCL10 and low levels of the B-cell-active chemokine CXCL13, whereas lymphocytoma lesions had high levels of CXCL13 and lower levels of CXCL9 and CXCL10. This pattern of chemokine expression was consistent with leukocyte marker mRNA in lesional skin. Moreover, using immunohistologic methods, CD3+ T cells and CXCL9 were visualized in erythema migrans and acrodermatitis lesions, and CD20+ B cells and CXCL13 were seen in lymphocytoma lesions. Thus, erythema migrans and acrodermatitis chronica atrophicans have high levels of the T-cell-active chemokines CXCL9 and CXCL10, whereas borrelial lymphocytoma has high levels of the B-cell-active chemokine CXCL13.

Lyme borreliosis

2013 ◽  
pp. 772-777
Author(s):  
Andreas Krause ◽  
Volker Fingerle
Keyword(s):  
Lyme Borreliosis ◽  
Erythema Migrans ◽  
Clinical Manifestations ◽  
Lyme Arthritis ◽  
Symptomatic Therapy ◽  
Positive Serology ◽  
Antibiotic Resistant ◽  
Acrodermatitis Chronica Atrophicans ◽  
Rapid Healing ◽  
The Central Nervous System

Lyme borreliosis (LB) is a multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi. The most frequent clinical manifestations include erythema migrans, meningoplyneuritis, and arthritis. Diagnosis of LB is made on clinical grounds and usually supported by a positive serology. Early diagnosis and treatment almost always leads to a rapid healing of the disease. However, in late manifestations gradual remission of symptoms may take several weeks to months. In rare cases, the pathogen can persist for many years or induce a persisting immunopathological response that may cause acrodermatitis chronica atrophicans, chronic neuroborreliosis of the central nervous system, or antibiotic resistant Lyme arthritis. However, even these chronic manifestations usually slowly regress after thorough antibiotic and symptomatic therapy, although in part with irreversible organ defects.

Lyme borreliosis

2013 ◽  
Author(s):  
Andreas Krause ◽  
Volker Fingerle
Keyword(s):  
Lyme Borreliosis ◽  
Erythema Migrans ◽  
Clinical Manifestations ◽  
Lyme Arthritis ◽  
Symptomatic Therapy ◽  
Positive Serology ◽  
Antibiotic Resistant ◽  
Acrodermatitis Chronica Atrophicans ◽  
Rapid Healing ◽  
The Central Nervous System

Lyme borreliosis (LB) is a multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi. The most frequent clinical manifestations include erythema migrans, meningoplyneuritis, and arthritis. Diagnosis of LB is made on clinical grounds and usually supported by a positive serology. Early diagnosis and treatment almost always leads to a rapid healing of the disease. However, in late manifestations gradual remission of symptoms may take several weeks to months. In rare cases, the pathogen can persist for many years or induce a persisting immunopathological response that may cause acrodermatitis chronica atrophicans, chronic neuroborreliosis of the central nervous system, or antibiotic resistant Lyme arthritis. However, even these chronic manifestations usually slowly regress after thorough antibiotic and symptomatic therapy, although in part with irreversible organ defects.

ERβ mRNA expression in ERα-negative and triple-negative breast cancers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 574-574
Author(s):  
Young Choi ◽  
Hadong Kim ◽  
Tae-Hoon Kim
Keyword(s):  
Cyclin D1 ◽  
Mrna Expression ◽  
Triple Negative ◽  
Lymph Node Status ◽  
Mrna Levels ◽  
Nuclear Staining ◽  
Breast Cancers ◽  
Proliferating Cells ◽  
Ki 67 ◽  
Reverse Transcription Pcr

574 Background: ERα is the main prognostic and therapeutic marker in breast cancer (BC). About 30% of BC cases are negative for ER (ERα-) and do not benefit from antiestrogen therapy (TAM). We aim to study ER-beta (ERβ) expression in ERα- and triple negative (TN) cancers to explore alternate pathway of treatment in this cohort. Methods: We studied 67 ERα- BC cases including 44 TN together with 74 ERα +BC cases obtained from patients aged 29 to 97 years old between 2003 and 2010. The histology included 110 intraductal, 12 medullary and 19 other types. 78 cases were grade 3, 52 were grade 2, and 11 were grade 1. RNA was extracted from FFPE and mRNA levels of ERβ isoform and ERα were determined by real-time quantitative reverse transcription PCR. IHC stains were done on TMA the sections for ERα, PR, Her-2, Ki-67, CK5/6 and Cyclin D1. Results: ERβ isoforms were highly expressed in ERα-, TN, basal-like and HER2 type BC cases. ERβ2 was the major ERβ variant expressed. Ki-67 proliferating cells (>20% nuclear staining) were mostly in ERα- rather than ERα+ cases (69.0% vs. 31.0%) as were cyclin D1- cells (82.2% vs. 17.8%). On the other hand, in ERα+ BC, ERα mRNA expression was consistently high and upregulated, and ERβ, low and down regulated, and the ratio of ERα+ to ERβ+ ranged from 3 to 100. ERβ1, 2 and 5 were co-expressed with ERα in 56%, 63%, and 30% of cases, respectively. Overall, ERβ mRNA levels did not show any significant correlation with age, tumor size, lymph node status and histological grades. Conclusions: ERβ-dependent proliferating tumor cells may render them more sensitive to TAM, and increase the effectiveness of TAM and its metabolites in ERα- and TN cases. Increased overall survival after adjuvant TAM ERα-BC may be directly related to ERβ over-expression. ERβ isoform is potential selective therapeutic target in a sub-cohort of ERα- BC. Additionally, when ERβ and ERα are co-expressed, ERβ appears to play a distinct role from its action in ERα- BC. [Table: see text]

scholarly journals TFL Deletion Induces Incredible CXCL13 Secretion and Cachexia in Vavp-Bcl2Transgenic Mice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3908-3908
Author(s):  
Kentaro Minagawa ◽  
Kanako Wakahashi ◽  
Fukui Chie ◽  
Shinichiro Nishikawa ◽  
Noboru Asada ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
T Cell ◽  
B Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Lineage ◽  
Body Weight Loss ◽  
Wild Type ◽  
B Cell Lymphomas

Abstract Diffuse large B-cell lymphomas (DLBCL) are heterogeneous diseases caused by several genetic aberrations. The novel post-transcriptional regulator gene called transformed follicular lymphoma (TFL) was first identified from t(2;6)(p12;q23), which appeared during the transformation of FL to DLBCL (Minagawa et al. Br J Haematol 2007). Normal human lymphocytes generally express TFL, but it is defective in some leukemia/lymphoma cell lines. TFL overexpression in such cell lines inhibited cell growth, suggesting that TFL functions as a tumor suppressor (Minagawa et al. Mol Cancer Res 2009). TFL locates in mRNA processing body in the cytoplasm and has the unique CCCH-type zinc finger motif functioning as RNase. TFL regulates several cytokines, including IL-2, IL-6, IL-10, TNF-α, and IL-17a, via mRNA degradation. In an experimental autoimmune encephalitis model, TFL null mice (TFL-/-) demonstrated persistent paralysis, resulting from more infiltration of Th17 cells into CNS with markedly increased IL-17a mRNA levels. Therefore, a TFL-driven feedback mechanism for excessive inflammation is indispensable to suppress T-cell-mediated autoimmune diseases (Minagawa et al. J Immunol 2014). TFL deletion examined by FISH using a 110kbp DNA probe containing an entireTFL locus was found in 12.8% of mature B-cell lymphomas (n=86, FL=30, DLBCL=40). However, the pathological significance of TFL deletion has not yet been clarified. To investigate how TFL loss affects lymphoma biology, we developed VavP-bcl2 transgenic (Bcl2-Tg)/TFL-/-mice. Although the survival of TFL-/- was comparable to the wild-type, Bcl2-Tg/TFL-/- died about 19 weeks earlier than Bcl2-Tg (Fig. 1). Both strains developed lymphadenopathy and splenomegaly similarly. No different microscopic finding was noted in lymph nodes, spleen, or bone marrow (BM). No additional malignancy was found in Bcl2-Tg/TFL-/- on autopsy. However, significant body weight loss appeared by 30 weeks in Bcl2-Tg/TFL-/- but not in Bcl2-Tg (Fig. 3). To identify what causes earlier death in Bcl2-Tg/TFL-/-, we carefully examined the phenotypic change of BM lymphocytes. We found a unique B220-IgM+ population in Bcl2-Tg BM, which was not found in wild-type. We speculated that TFL deficiency in this population might drive the deterioration in Bcl2-Tg/TFL-/-. To identify which mRNA was dysregulated by TFL deficiency, we comprehensively analyzed mRNA expression profiles in B220-IgM+ cells in both strains using cDNA microarray chip. Among several genes upregulated at least threefold in Bcl2-Tg/TFL-/- than Bcl2-Tg, we paid attention to CXCL13, the mRNA expression of which in Bcl2-Tg/TFL-/- was 4.19-fold higher than that in Bcl2-Tg (p=0.03). In fact, CXCL13 concentration in BM extracellular fluid as well as plasma in Bcl2-Tg/TFL-/- showed incredible increase in a logarithmic scale (Fig. 2). As a noteworthy event, body weight loss in Bcl2-Tg/TFL-/- followed the increase of CXCL13 in plasma by 30 weeks (Fig. 3). To confirm that TFL post-transcriptionally regulates CXCL13 mRNA through the degradation of its 3′UTR, we performed a reporter assay with a plasmid vector containing 3′UTR of CXCL13 mRNA. Co-transfection with a TFL expression vector showed decreased luciferase activity compared to the control. This suggests that TFL directly regulates CXCL13 mRNA via its 3′UTR degradation. This regulation occurs more prominently in B-cell lineage rather than myeloid or T-cell lineage, whereas IL-2 mRNA regulation occurs promiscuously. CXCL13 secretion was significantly increased in the culture supernatant of BM cells but not spleen cells derived from Bcl2-Tg/TFL-/-. We further sorted several cell populations, including B220-IgM+ in BM, and cultured them for 96 h. CXCL13 secretion from B220-IgM+ population was increased significantly compared to other populations. Thus, we concluded that B220-IgM+ cells in BM are the main producer of CXCL13 in Bcl2-Tg/TFL-/-. Loss of TFL-driven attenuation for excessive inflammation in lymphoma-bearing mice could contribute to the short survival. It is of interest whether high plasma CXCL13 directly affects cachexia and early death in Bcl2-Tg/TFL-/-. TFL deletion in human lymphoma might contribute not only to malignant transformation but also to a major B symptom, i.e., weight loss. Our findings may open a new window for the predictive factor on the prognosis of B-cell lymphoma and/or new therapeutic intervention by targeting CXCL13. Disclosures No relevant conflicts of interest to declare.

scholarly journals Oxidized-ATP Attenuates Kidney Allograft Rejection By Inhibiting T-Cell, B-Cell, and Macrophage Activity

Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 106-114
Author(s):  
Xiang Ding ◽  
Nancy A. Wilson ◽  
Robert R. Redfield ◽  
Sarah E. Panzer ◽  
Bret Verhoven ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Allograft Rejection ◽  
Brown Norway ◽  
Solid Organ ◽  
Mrna Levels ◽  
Kidney Allograft ◽  
Macrophage Activity ◽  
Kidney Allograft Rejection

BackgroundExtracellular ATP binds to purinergic receptors and promotes inflammatory responses. We tested whether oxidized ATP (oATP), P2X7 receptor antagonist can attenuate acute kidney allograft rejection.MethodsBrown Norway kidney allografts were transplanted into Lewis recipients. Three groups were defined: oATP (n=8), cyclosporine A (n=6), and no treatment (n=8). On day 7, we assessed kidney allograft survival, function, and rejection characteristics. We further determined T-cell, B-cell, and macrophage response to oATP in vivo and in vitro and examined intragraft inflammatory gene transcripts.ResultsKaplan–Meier survival analyses demonstrated significantly better graft survival rates in oATP and CsA groups compared with no treatment (P<0.05). Similarly, serum creatinine (Scr) and BUN levels were significantly lower in oATP and CsA groups (P<0.05). oATP reduced both T cell–mediated rejection and antibody-mediated rejection, inhibited B-cell and T-cell activation, and downregulated intragraft IL-6 mRNA levels (P<0.0001). In vitro, oATP prevented proliferation in mixed lymphocyte reaction assays, and inhibited macrophage P2X7R activity in a dose-dependent manner.ConclusionsOur findings suggest that oATP mitigates kidney allograft rejection by inhibiting T-cell, B-cell, and macrophage activity and indicate a potential role for the purinergic system and oATP in solid organ transplantation.

scholarly journals Disseminated and chronic Lyme borreliosis in Norway, 1995 – 2004

2005 ◽  
Vol 10 (10) ◽  
pp. 1-2 ◽  
Author(s):  
K Nygård ◽  
A B Brantsaeter ◽  
R Mehl
Keyword(s):  
Lyme Borreliosis ◽  
Erythema Migrans ◽  
Clinical Manifestations ◽  
Laboratory Diagnosis ◽  
Incidence Rates ◽  
Tick Bites ◽  
Serological Tests ◽  
Clear Trend ◽  
Acrodermatitis Chronica Atrophicans ◽  
Insect Repellents

Lyme borreliosis is the most common tickborne infection in Norway. All clinical manifestations of Lyme borreliosis other than erythema migrans are notifiable to Folkehelseinstituttet, the Norwegian Institute of Public Health. During the period 1995-2004 a total of 1506 cases of disseminated and chronic Lyme borreliosis were reported. Serological tests were the basis for laboratory diagnosis in almost all cases. The annual numbers of cases showed no clear trend over the period, but varied each year between 120 and 253 cases, with the highest number of cases reported in 2004. Seventy five per cent of cases with information on time of onset were in patients who fell ill during the months of June to October. There was marked geographical variation in reported incidence rates, with the highest rates reported from coastal counties in southern and central Norway. Fifty six per cent of the cases were in males and 44% in females. The highest incidence rate was found in children aged between 5 and 9 years. Neuroborreliosis was the most common clinical manifestation (71%), followed by arthritis/arthralgia (22%) and acrodermatitis chronica atrophicans (5%). Forty six per cent of patients were admitted to hospital. Prevention of borreliosis in Norway relies on measures to prevent tick bites, such as use of protective clothing and insect repellents, and early detection and removal of ticks. Antibiotics are generally not recommended for prophylaxis after tick bites in Norway.

scholarly journals Peptide-Based OspC Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Lyme Borreliosis

1998 ◽  
Vol 36 (12) ◽  
pp. 3474-3479 ◽  
Author(s):  
Marianne J. Mathiesen ◽  
Michael Christiansen ◽  
Klaus Hansen ◽  
Arne Holm ◽  
Eva Åsbrink ◽  
...  
Keyword(s):  
Lyme Borreliosis ◽  
Immunosorbent Assay ◽  
Erythema Migrans ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amino Acid Residues ◽  
Serum Samples ◽  
Igg Antibody ◽  
Acrodermatitis Chronica Atrophicans ◽  
Increased Sensitivity

Sera from 210 patients with Lyme borreliosis (LB) were studied by an enzyme-linked immunosorbent assay (ELISA) based on a synthetic peptide (pepC10) comprising the C-terminal 10-amino-acid residues of OspC of Borrelia burgdorferi. We found that 36.3 and 45.0% of the serum samples from patients with erythema migrans (EM) and neuroborreliosis (NB), respectively, displayed immunoglobulin M (IgM) anti-pepC10 reactivities, while these samples rarely (≤8%) displayed IgG antibody reactivities. Sera from patients with acrodermatitis chronica atrophicans did not contain anti-pepC10 antibodies. The diagnostic performance of this newly developed peptide ELISA was compared with those of an ELISA based on the full-length recombinant OspC protein (rOspC) and a commercially available ELISA based on theB. burgdorferi flagellum (Fla). The sensitivity of the IgM pepC10 ELISA was slightly lower (P < 0.04) than that of the rOspC ELISA for EM patients (36.3 versus 43.8%), while there was no difference for NB patients (45.0 versus 48.0%). However, the optical density values obtained by the pepC10 ELISA were generally higher than those obtained by the rOspC ELISA, leading to a significantly better quantitative discrimination between seropositive patients with NB and controls (P < 0.008). The specificity of the pepC10 ELISA was similar to those of the rOspC ELISA and the Fla ELISA for relevant controls including patients with syphilis and mononucleosis. Although the overall diagnostic sensitivity of the Fla ELISA was superior, 8.8 and 12.0% of the EM and NB patients, respectively, were antibody positive only by the pepC10 ELISA. Thus, use of a diagnostic test for LB based on the detection of IgM antibodies to pepC10 and Fla has increased sensitivity for the diagnosis of early LB.

Ontogeny of the expression and regulation of interleukin-6 (IL-6) and IL-1 mRNAs by human trophoblast cells during differentiation in vitro

1995 ◽  
Vol 147 (3) ◽  
pp. 487-496 ◽  
Author(s):  
A Stephanou ◽  
L Myatt ◽  
A L W Eis ◽  
N Sarlis ◽  
H Jikihara ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Internal Control ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Human Trophoblast ◽  
Reverse Transcription Pcr ◽  
Cytotrophoblast Cells ◽  
Almost All

Abstract During human placental differentiation, mononuclear cytotrophoblast cells fuse and differentiate into syncytiotrophoblast cells. Although syncytiotrophoblast cells have been shown to express interleukin-1α (IL-1α), IL-1β and IL-6, the pattern of expression of these cytokines during placental differentiation is unknown. We have examined the expression of IL-1α, IL-1β and IL-6 mRNA during differentiation of cytotrophoblast cells in culture. IL-1α, IL-1β and IL-6 mRNA levels were determined by semiquantitative reverse transcription-PCR analysis using glyceraldehyde phosphate dehydrogenase as an internal control. All three cytokine mRNA levels decreased markedly during trophoblast differentiation. After 6 days in culture, when almost all the cytotrophoblast cells had fused and differentiated into syncytiotrophoblast cells, the amounts of IL-1α, IL-1β and IL-6 mRNA were decreased by 87·1, 72·1 and 60·9% respectively. Exogenous IL-6 had differential effects on cytokine mRNA expression. When added to placental cultures during the first 6 days of culture, IL-6 markedly inhibited IL-6, IL-1α and IL-1β mRNA expression. However, when added to the cells during days 6–9 of culture, when most of the cells were syncytiotrophoblast cells, IL-6 stimulated IL-lα and IL-1β mRNA expression. The results of these studies indicate that IL-1α, IL-1β and IL-6 mRNA expression decreases markedly during cytotrophoblast differentiation in vitro and that the regulation of trophoblast cytokine mRNA levels changes during differentiation. Journal of Endocrinology (1995) 147, 487–496

scholarly journals Distribution and kinetics of superantigen-induced cytokine gene expression in mouse spleen.

1993 ◽  
Vol 178 (5) ◽  
pp. 1531-1539 ◽  
Author(s):  
M Bette ◽  
M K Schäfer ◽  
N van Rooijen ◽  
E Weihe ◽  
B Fleischer
Keyword(s):  
T Cell ◽  
Mrna Expression ◽  
Interleukin 2 ◽  
Cytokine Gene Expression ◽  
Tnf Alpha ◽  
Second Phase ◽  
Mrna Levels ◽  
Messenger Rnas ◽  
Kinetics Of

The polyclonal stimulation of T cells by bacterial superantigens is involved in the pathogenesis of the toxic shock syndrome in certain staphylococcal and streptococcal infections. Here we describe the onset and kinetics of superantigen-induced cytokine production in situ in spleens of normal BALB/c mice monitored at the level of cytokine mRNA expression by in situ hybridization. Messenger RNAs for interleukin 2 (IL-2), interferon gamma, and tumor necrosis factors (TNF) alpha and beta were not expressed at detectable levels in spleens of unstimulated animals but became visible already 30 min after intraperitoneal application of 50 micrograms staphylococcal enterotoxin B. All mRNA levels showed peak expression approximately 3 h after injection and a slow decrease up to 24 h after injection. Expression of the mRNAs was restricted to the T cell-dependent area of the periarteriolar lymphatic sheets of the spleen. Interestingly, TNF-alpha mRNA showed a biphasic response, the early appearing mRNA had the same localization as the other mRNAs, whereas after 3 h TNF-alpha mRNA showed a broader distribution indicating a second cell population producing TNF-alpha. The expression of IL-2 and TNF proteins in the serum increased in parallel to the observed mRNA changes with a slight delay. The presence of macrophages was not required for the expression of the cytokine mRNAs in the spleen as the expression was unchanged in macrophage-depleted mice. Only the second phase of TNF-alpha mRNA expression was abrogated in such animals. The expression of all mRNAs was completely suppressed by prior administration of cyclosporin A. These data show that nonphagocytic cells are the essential superantigen-presenting cells in vivo and indicate that at least part of the pathogenetic TNF-alpha is T cell derived.

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