Increased Milk Levels of Transforming Growth Factor-α, β1, and β2 During Escherichia coli-Induced Mastitis

Among the gram-negative bacteria that cause mastitis, Escherichia coli are the most prevalent. The innate immune system provides initial protection against E. coli infection by detecting the presence of the foreign pathogens and by mounting an inflammatory response, the latter of which is mediated by cytokines such as IL-1β, IL-8, and tumor necrosis factor (TNF)-α. Although changes in these cytokines during mastitis have been well-described, it is believed that other mediators moderate mammary gland inflammatory responses as well. The growth factors/cytokines transforming growth factor (TGF)-α, TGF-β1, and TGF-β2 are all expressed in the mammary gland and have been implicated in regulating mammary gland development. In other tissues, these growth factors/cytokines have been shown to moderate inflammation. The objective of the current study was to determine whether TGF-α, TGF-β1, and TGF-β2 milk concentrations were altered during the course of E. coli-induced mastitis. The contralateral quarters of 11 midlactating Holstein cows were challenged with either saline or 72 cfu of E. coli, and milk samples were collected. Basal milk levels of TGF-α, TGF-β1, and TGF-β2 were 98.81 ± 22.69 pg/mL, 3.35 ± 0.49 ng/mL, and 22.36 ± 3.78 ng/mL, respectively. Analysis of whey samples derived from E. coli-infected quarters revealed an increase in milk levels of TGF-α within 16 h of challenge, and these increases persisted for an additional 56 h. Elevated TGF-β1 and TGF-β2 milk concentrations were detected in E. coli-infected quarters 32 h after challenge, and these elevations were sustained throughout the study. Because TGF-α, TGF-β1, and TGF-β2 have been implicated in mediating inflammatory processes, their induction during mastitis is consistent with a role for these molecules in mediating mammary gland host innate immune responses to infection.

[1]  M. Paape,et al.  Escherichia coli and Staphylococcus aureus Elicit Differential Innate Immune Responses following Intramammary Infection , 2004, Clinical Diagnostic Laboratory Immunology.

[2]  T. Ganz,et al.  Wound Healing and Expression of Antimicrobial Peptides/Polypeptides in Human Keratinocytes, a Consequence of Common Growth Factors1 , 2003, The Journal of Immunology.

[3]  Wayne L. Smith,et al.  The cytokine markers in Staphylococcus aureus mastitis of bovine mammary gland. , 2003, Journal of veterinary medicine. B, Infectious diseases and veterinary public health.

[4]  D. Proud,et al.  Effects of tumor necrosis factor-α, epidermal growth factor and transforming growth factor-α on interleukin-8 production by, and human rhinovirus replication in, bronchial epithelial cells , 2001 .

[5]  P. Rainard,et al.  Cell subpopulations and cytokine expression in cow milk in response to chronic Staphylococcus aureus infection. , 2001, Journal of dairy science.

[6]  S. Wenzel,et al.  Peripheral blood and airway tissue expression of transforming growth factor beta by neutrophils in asthmatic subjects and normal control subjects. , 2000, The Journal of allergy and clinical immunology.

[7]  P. Rainard,et al.  Differential Induction of Complement Fragment C5a and Inflammatory Cytokines during Intramammary Infections withEscherichia coli and Staphylococcus aureus , 2000, Clinical Diagnostic Laboratory Immunology.

[8]  G. Ashcroft Bidirectional regulation of macrophage function by TGF-β , 1999 .

[9]  R. Pakkanen,et al.  Determination of Transforming Growth Factor-β1 (TGF-β1) and Insulin-Like Growth Factor 1 (IGF-1) in Bovine Colostrum Samples , 1998 .

[10]  Anita B. Roberts,et al.  REGULATION OF IMMUNE RESPONSES BY TGF-β* , 1998 .

[11]  R. Pakkanen Determination of transforming growth factor-beta 2 (TGF-beta 2) in bovine colostrum samples. , 1998, Journal of immunoassay.

[12]  C. Dinarello,et al.  Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock. , 1997, Chest.

[13]  D. Wilson,et al.  Bovine mastitis pathogens in New York and Pennsylvania: prevalence and effects on somatic cell count and milk production. , 1997, Journal of dairy science.

[14]  L. Sheffield Mastitis increases growth factor messenger ribonucleic acid in bovine mammary glands. , 1997, Journal of dairy science.

[15]  J. Calafat,et al.  Human monocytes and neutrophils store transforming growth factor-alpha in a subpopulation of cytoplasmic granules. , 1997, Blood.

[16]  T. J. Yang,et al.  The Regulatory Role of Transforming Growth Factor‐Beta in Activation of Milk Mononuclear Cells , 1997, American journal of reproductive immunology.

[17]  M. Choudhry,et al.  Transforming growth factor‐β negatively modulates T‐cell responses in sepsis , 1997 .

[18]  M. Giedlin,et al.  IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. , 1995, Journal of immunology.

[19]  D. Hoyt,et al.  Tumor necrosis factor antibody treatment of septic baboons reduces the production of sustained T-cell suppressive factors. , 1995, Shock.

[20]  D. Foreman,et al.  Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents. , 1994, Journal of cell science.

[21]  T. Casale,et al.  Pulmonary epithelial cells facilitate TNF-alpha-induced neutrophil chemotaxis. A role for cytokine networking. , 1994, Journal of immunology.

[22]  K. Bry Epidermal growth factor and transforming growth factor-alpha enhance the interleukin-1- and tumor necrosis factor-stimulated prostaglandin E2 production and the interleukin-1 specific binding on amnion cells. , 1993, Prostaglandins, leukotrienes, and essential fatty acids.

[23]  C. Sarraf,et al.  Transforming growth factor‐α immunoreactivity in a variety of epithelial tissues , 1993 .

[24]  Y. Vodovotz,et al.  Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. , 1992, The Journal of biological chemistry.

[25]  P. Schmid,et al.  Localization of transforming growth factor-β1, -β2 and -β3 gene expression in bovine mammary gland , 1991, Molecular and Cellular Endocrinology.

[26]  R. Knecht,et al.  Separation, purification, and sequence identification of TGF-β1 and TGF-β2 from bovine milk , 1991 .

[27]  J. Orenstein,et al.  Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome , 1991, The Journal of experimental medicine.

[28]  K. Ostensson,et al.  Flow cytofluorometric studies on the alteration of leukocyte populations in blood and milk during endotoxin-induced mastitis in cows. , 1990, American journal of veterinary research.

[29]  M. Sporn,et al.  Induction of transforming growth factor-α in activated human alveolar macrophages , 1988, Cell.

[30]  M. Paape,et al.  In vitro study of polymorphonuclear leukocyte damage to mammary tissues of lactating cows. , 1986, American journal of veterinary research.

[31]  D. Proud,et al.  Effects of tumor necrosis factor-alpha, epidermal growth factor and transforming growth factor-alpha on interleukin-8 production by, and human rhinovirus replication in, bronchial epithelial cells. , 2001, International immunopharmacology.

[32]  S. Robinson,et al.  The transforming growth factors beta in development and functional differentiation of the mouse mammary gland. , 2001, Advances in experimental medicine and biology.

[33]  C. Wagner,et al.  The effect of pasteurization on transforming growth factor alpha and transforming growth factor beta 2 concentrations in human milk. , 2001, Advances in experimental medicine and biology.

[34]  G. Ashcroft Bidirectional regulation of macrophage function by TGF-beta. , 1999, Microbes and infection.

[35]  A. Roberts,et al.  Regulation of immune responses by TGF-beta. , 1998, Annual review of immunology.

[36]  R. Pakkanen,et al.  Determination of transforming growth factor-beta 1 (TGF-beta 1) and insulin-like growth factor (IGF-1) in bovine colostrum samples. , 1998, Journal of immunoassay.

[37]  M. Frazier-Jessen,et al.  TGF-beta: a balancing act. , 1998, International reviews of immunology.

[38]  M. Choudhry,et al.  Transforming growth factor-beta negatively modulates T-cell responses in sepsis. , 1997, FEBS letters.

[39]  T. Wright,et al.  Cytokines in acute and chronic inflammation. , 1997, Frontiers in bioscience : a journal and virtual library.

[40]  A. Manning,et al.  TGF-beta 1, IL-10 and IL-4 differentially modulate the cytokine-induced expression of IL-6 and IL-8 in human endothelial cells. , 1996, Cytokine.

[41]  A. Manning,et al.  TGF-β1, IL-10 and IL-4 differentially modulate the cytokine-induced expression of IL-6 and IL-8 in human endothelial cells , 1996 .

[42]  C. Sarraf,et al.  Transforming growth factor-alpha immunoreactivity in a variety of epithelial tissues. , 1993, Cell proliferation.

[43]  R. Derynck The Physiology Of Transforming Growth Factor-α , 1992 .

[44]  R. de Waal Malefyt,et al.  Functional characterization of human IL-10. , 1992, International archives of allergy and immunology.

[45]  P. Schmid,et al.  Localization of transforming growth factor-beta 1, -beta 2 and -beta 3 gene expression in bovine mammary gland. , 1991, Molecular and cellular endocrinology.

[46]  R. Knecht,et al.  Separation, purification, and sequence identification of TGF-beta 1 and TGF-beta 2 from bovine milk. , 1991, Journal of protein chemistry.

[47]  M. Sporn,et al.  Induction of transforming growth factor-alpha in activated human alveolar macrophages. , 1988, Cell.

[48]  R. Eberhart Coliform mastitis. , 1984, The Veterinary clinics of North America. Large animal practice.